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Frontiers in Neurology 2022It is widely acknowledged that central nervous system (CNS) infection is a serious infectious disease accompanied by various complications. However, the accuracy of...
OBJECTIVE
It is widely acknowledged that central nervous system (CNS) infection is a serious infectious disease accompanied by various complications. However, the accuracy of current detection methods is limited, leading to delayed diagnosis and treatment. In recent years, metagenomic next-generation sequencing (mNGS) has been increasingly adopted to improve the diagnostic yield. The present study sought to evaluate the value of mNGS in CNS infection diagnosis.
METHODS
Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2022 guidelines, we searched relevant articles published in seven databases, including PubMed, Web of Science, and Cochrane Library, published from January 2014 to January 2022. High-quality articles related to mNGS applications in the CNS infection diagnosis were included. The comparison between mNGS and the gold standard of CNS infection, such as culture, PCR or serology, and microscopy, was conducted to obtain true positive (TP), true negative (TN), false positive (FP), and false negative (FN) values, which were extracted for sensitivity and specificity calculation.
RESULTS
A total of 272 related studies were retrieved and strictly selected according to the inclusion and exclusion criteria. Finally, 12 studies were included for meta-analysis and the pooled sensitivity was 77% (95% CI: 70-82%, = 39.69%) and specificity was 96% (95% CI: 93-98%, = 72.07%). Although no significant heterogeneity in sensitivity was observed, a sub-group analysis was conducted based on the pathogen, region, age, and sample pretreatment method to ascertain potential confounders. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for CNS infection was 0.91 (95% CI: 0.88-0.93). Besides, Deek's Funnel Plot Asymmetry Test indicated no publication bias in the included studies (, > 0.05).
CONCLUSION
Overall, mNGS exhibits good sensitivity and specificity for diagnosing CNS infection and diagnostic performance during clinical application by assisting in identifying the pathogen. However, the efficacy remains inconsistent, warranting subsequent studies for further performance improvement during its clinical application.
STUDY REGISTRATION NUMBER
INPLASY202120002.
PubMed: 36203993
DOI: 10.3389/fneur.2022.989280 -
Frontiers in Cellular and Infection... 2022() is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with in recent years. The disseminated infection of...
() is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with in recent years. The disseminated infection of can be life-threatening without timely and effective antifungal therapy. Rapid and accurate pathogenic microbiological diagnosis is particularly critical for these patients. A total of 505 patients with IEI were admitted to our hospital between January 2019 and June 2022, among whom was detected in 6 patients by metagenomic next-generation sequencing (mNGS), and their clinical and immunological characteristics were summarized. We performed a systematic literature review on infections with published immunodeficiency-related gene mutations. All patients in our cohort were confirmed to have genetic mutations in , , , , and . was detected in both the blood and lymph nodes of P1 with mutations, and the clinical manifestations were serious and included recurrent fever, weight loss, severe anemia, splenomegaly and lymphadenopathy, all requiring long-term antifungal therapy. These six patients received antifungal treatment, which relieved symptoms and improved imaging findings. Five patients survived, while one patient died of sepsis after hematopoietic stem cell transplantation. The application of mNGS methods for pathogen detection in IEI patients and comparison with traditional diagnosis methods were investigated. Traditional diagnostic methods and mNGS tests were performed simultaneously in 232 patients with IEI. Compared to the traditional methods, the sensitivity and specificity of mNGS in diagnosing infection were 100% and 98.7%, respectively. The reporting time for detection was approximately 26 hours by mNGS, 3-14 days by culture, and 6-11 days by histopathology. infection was first reported in IEI patients with gene mutation, which expanded the IEI lineage susceptible to . For IEI patients with infection, we highlight the application of mNGS in pathogenic detection. mNGS is recommended as a front-line diagnostic test for rapidly identifying pathogens in complex and severe infections.
Topics: Antifungal Agents; China; High-Throughput Nucleotide Sequencing; Humans; Mycoses; Talaromyces; Technology
PubMed: 36159645
DOI: 10.3389/fcimb.2022.987692 -
Frontiers in Physiology 2022Microbiotas are the range of microorganisms (mainly bacteria and fungi) colonizing multicellular, macroscopic organisms. They are crucial for several metabolic functions...
Microbiotas are the range of microorganisms (mainly bacteria and fungi) colonizing multicellular, macroscopic organisms. They are crucial for several metabolic functions affecting the health of the host. However, difficulties hamper the investigation of microbiota composition in cultivating microorganisms in standard growth media. For this reason, our knowledge of microbiota can benefit from the analysis of microbial macromolecules (DNA, transcripts, proteins, or by-products) present in various samples collected from the host. Various omics technologies are used to obtain different data. Metagenomics provides a taxonomical profile of the sample. It can also be used to obtain potential functional information. At the same time, metatranscriptomics can characterize members of a microbiome responsible for specific functions and elucidate genes that drive the microbiotas relationship with its host. Thus, while microbiota refers to microorganisms living in a determined environment (taxonomy of microorganisms identified), microbiome refers to the microorganisms and their genes living in a determined environment and, of course, metagenomics focuses on the genes and collective functions of identified microorganisms. Metabolomics completes this framework by determining the metabolite fluxes and the products released into the environment. The gallbladder is a sac localized under the liver in the human body and is difficult to access for bile and tissue sampling. It concentrates the bile produced in the hepatocytes, which drains into bile canaliculi. Bile promotes fat digestion and is released from the gallbladder into the upper small intestine in response to food. Considered sterile originally, recent data indicate that bile microbiota is associated with the biliary tract's inflammation and carcinogenesis. The sample size is relevant for omic studies of rare diseases, such as gallbladder carcinoma. Although in its infancy, the study of the biliary microbiota has begun taking advantage of several omics strategies, mainly based on metagenomics, metabolomics, and mouse models. Here, we show that omics analyses from the literature may provide a more comprehensive image of the biliary microbiota. We review studies performed in this environmental niche and focus on network-based approaches for integrative studies.
PubMed: 36111147
DOI: 10.3389/fphys.2022.888233 -
Microorganisms Aug 2022Our systematic review aimed to evaluate the effect of periodontal interventions on the diversity and composition of periodontal microbiota assessed by high throughput...
Our systematic review aimed to evaluate the effect of periodontal interventions on the diversity and composition of periodontal microbiota assessed by high throughput sequencing (HTS) metagenomics analysis. An electronic search was conducted from database inception to November 2021. All clinical trials that evaluated the effect of periodontal interventions on the gingival microbiota through HTS were selected. The measures of alpha diversity, richness, Shannon diversity index, and the Chao1 index, were used as the primary outcome, whereas relative abundances of bacterial genera were considered as the secondary outcome. Overall, 24 studies were eligible for the systematic review, of which 13 studies were included in the meta-analysis. Periodontal intervention for the test group decreased Shannon diversity, richness, and Chao1 index (alpha diversity), as observed from baseline to post-treatment. The most common genera that increased after periodontal therapy were , , , , and , whilst , , , and decreased after periodontal therapy. Periodontal interventions may decrease the bacterial diversity and richness and alter the composition of oral microbiota in the short term. Periodontal microbiota signatures could potentially be used for the assessment of periodontal disease development, progression, and success of the intervention.
PubMed: 36014000
DOI: 10.3390/microorganisms10081582 -
The Lancet. Microbe Nov 2022Data from animal models suggest a role of early-life gut microbiota in lung immune development, and in establishing susceptibility to respiratory infections and asthma... (Review)
Review
Data from animal models suggest a role of early-life gut microbiota in lung immune development, and in establishing susceptibility to respiratory infections and asthma in humans. This systematic review summarises the association between infant (ages 0-12 months) gut microbiota composition measured by genomic sequencing, and childhood (ages 0-18 years) respiratory diseases (ie, respiratory infections, wheezing, or asthma). Overall, there was evidence that low α-diversity and relative abundance of particular gut-commensal bacteria genera (Bifidobacterium, Faecalibacterium, Ruminococcus, and Roseburia) are associated with childhood respiratory diseases. However, results were inconsistent and studies had important limitations, including insufficient characterisation of bacterial taxa to species level, heterogeneous outcome definitions, residual confounding, and small sample sizes. Large longitudinal studies with stool sampling during the first month of life and shotgun metagenomic approaches to improve bacterial and fungal taxa resolution are needed. Standardising follow-up times and respiratory disease definitions and optimising causal statistical approaches might identify targets for primary prevention of childhood respiratory diseases.
Topics: Infant; Humans; Infant, Newborn; Child, Preschool; Child; Adolescent; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Feces; Bacteria; Asthma; Respiration Disorders; Respiratory Tract Infections
PubMed: 35988549
DOI: 10.1016/S2666-5247(22)00184-7 -
Asia Pacific Allergy Jul 2022Individual studies have suggested that upper airway dysbiosis may be associated with asthma or its severity. We aimed to systematically review studies that evaluated... (Review)
Review
Individual studies have suggested that upper airway dysbiosis may be associated with asthma or its severity. We aimed to systematically review studies that evaluated upper airway bacterial microbiota in relation to asthma, compared to nonasthmatic controls. Searches used MEDLINE, Embase, and Web of Science Core Collection. Eligible studies included association between asthma and upper airway dysbiosis; assessment of composition and diversity of upper airway microbiota using 16S rRNA or metagenomic sequencing; upper airway samples from nose, nasopharynx, oropharynx or hypopharynx. Study quality was assessed and rated using the Newcastle-Ottawa scale. A total of 249 publications were identified; 17 in the final analysis (13 childhood asthma and 4 adult asthma). Microbiome richness was measured in 6 studies, species diversity in 12, and bacterial composition in 17. The quality of evidence was good and fair. The alpha-diversity was found to be higher in younger children with wheezing and asthma, while it was lower when asthmatic children had rhinitis or mite sensitization. In children, Proteobacteria and Firmicutes were higher in asthmatics compared to controls (7 studies), and , , and were predominant in the bacterial community. In pooled analysis, nasal colonization was associated with the presence of wheezing at age 5 ( = 0.04). In adult patients with asthma, the abundance of Proteobacteria was elevated in the upper respiratory tract (3 studies). Nasal colonization of was lower in asthmatics (2 studies). This study demonstrates the potential relationships between asthma and specific bacterial colonization in the upper airway in adult and children with asthma.
PubMed: 35966153
DOI: 10.5415/apallergy.2022.12.e32 -
International Journal of Infectious... Sep 2022Identifying pathogens in patients with pulmonary infection (PI) has always been a major challenge in medicine. Compared with sputum and throat swabs, bronchoalveolar... (Meta-Analysis)
Meta-Analysis Review
Diagnostic performance of metagenomic next-generation sequencing for the detection of pathogens in bronchoalveolar lavage fluid in patients with pulmonary infections: Systematic review and meta-analysis.
OBJECTIVES
Identifying pathogens in patients with pulmonary infection (PI) has always been a major challenge in medicine. Compared with sputum and throat swabs, bronchoalveolar lavage fluid (BALF) can better reflect the actual state of the lungs. However, there has not been a meta-analysis of the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) in detecting pathogens in BALF from patients with PIs.
METHODS
Data sources were PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure. The pooled sensitivity and specificity were estimated using random-effects or fixed-effect models. Subgroup analysis was performed to reveal the effect of potential explanatory factors on the diagnostic performance measures.
RESULTS
The pooled sensitivity was 78% (95% confidence interval [CI]: 67-87%; I = 92%) and the pooled specificity was 77% (95% CI: 64-94%; I = 74%) for mNGS. Subgroup analyses for the sensitivity of mNGS revealed that patients with PIs who were severely ill or immunocompromised significantly affected heterogeneity (P < 0.001). The positive detection rate of mNGS for pathogens in BALF of severely or immunocompromised pulmonary-infected patients was 92% (95% CI: 78-100%).
CONCLUSION
mNGS has high diagnostic performance for BALF pathogens in patients with PIs, especially in critically ill or immunocompromised patients.
Topics: Bronchoalveolar Lavage Fluid; High-Throughput Nucleotide Sequencing; Humans; Metagenome; Metagenomics; Pneumonia; Sensitivity and Specificity
PubMed: 35907477
DOI: 10.1016/j.ijid.2022.07.054 -
Clinical Microbiology and Infection :... Dec 2022The intestinal microbiome provides a reservoir for antibiotic resistance genes (ARGs). The neonatal microbiome is more susceptible to disturbance from external factors... (Review)
Review
BACKGROUND
The intestinal microbiome provides a reservoir for antibiotic resistance genes (ARGs). The neonatal microbiome is more susceptible to disturbance from external factors than the established microbiome in later life.
OBJECTIVES
In this review, we systematically summarize studies which investigated the intestinal resistome in neonates.
DATA SOURCES
MEDLINE and Embase databases were searched.
STUDY ELIGIBILITY CRITERIA
We included original studies which investigated ARGs in stool or rectal swabs in neonates using molecular diagnostics.
METHODS OF DATA SYNTHESIS
Two authors independently extracted data, which were summarized in tables.
RESULTS
Our search identified 2701 studies, of which 23 (22 cohorts) were included. The studies show that the neonatal intestine harbours a high abundance and variety of ARGs, even in the absence of direct antibiotic exposure. The most commonly found ARGs confer resistance to aminoglycosides, β-lactams, macrolides, tetracyclines, or multidrug resistance. There is evidence that ARGs can be transferred from mothers to neonates. Interestingly, however, compared to mothers, neonates are reported to have a higher abundance of ARGs. One likely reason for this is the bacterial phylogenetic composition with a high abundance of Gammaproteobacteria in neonatal stool. Factors that have been associated with a higher abundance of ARGs are intrapartum and neonatal antibiotic use. Breastfeeding and neonatal probiotic use have been associated with a lower abundance of ARGs. Antibiotics during pregnancy, delivery mode, or sex are reported to have little effect. However, this might be because studies were underpowered and because it is difficult to account for effect modifiers.
CONCLUSIONS
The neonatal intestine seems to have a lower colonization resistance, which could make it easier for antibiotic-resistant populations to establish themselves. Future studies will help in the development of evidence-based interventions to modulate the abundance of ARGs in neonates, for example, by the use of pre- and probiotics and bacteriophages.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Phylogeny; Drug Resistance, Microbial; Anti-Bacterial Agents; Bacteria; Intestines
PubMed: 35868586
DOI: 10.1016/j.cmi.2022.07.014 -
Frontiers in Cellular and Infection... 2022A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic method is particularly important for PJI. Recently, the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting PJI has attracted much attention, while the evidence of its accuracy is quite limited. Thus, this study aimed to evaluate the accuracy of mNGS for the diagnosis of PJI.
METHODS
We summarized published studies to identify the potential diagnostic value of mNGS for PJI patients by searching online databases using keywords such as "prosthetic joint infection", "PJI", and "metagenomic sequencing". Ten of 380 studies with 955 patients in total were included. The included studies provided sufficient data for the completion of 2-by-2 tables. We calculated the sensitivity, specificity, and area under the SROC curve (AUC) to evaluate mNGS for PJI diagnosis.
RESULTS
We found that the pooled diagnostic sensitivity and specificity of mNGS for PJI were 0.93 (95% CI, 0.83 to 0.97) and 0.95 (95% CI, 0.92 to 0.97), respectively. Positive and negative likelihood ratios were 18.3 (95% CI, 10.9 to 30.6) and 0.07 (95% CI, 0.03 to 0.18), respectively. The area under the curve was 0.96 (95% CI, 0.93 to 0.97).
CONCLUSION
Metagenomic next-generation sequencing displays high accuracy in the diagnosis of PJI, especially for culture-negative cases.
Topics: Arthritis, Infectious; High-Throughput Nucleotide Sequencing; Humans; Metagenomics; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid
PubMed: 35755833
DOI: 10.3389/fcimb.2022.875822 -
Frontiers in Medicine 2022The fight against (MTB) has been going on for thousands of years, while it still poses a threat to human health. In addition to routine detections, metagenomic...
The fight against (MTB) has been going on for thousands of years, while it still poses a threat to human health. In addition to routine detections, metagenomic next-generation sequencing (mNGS) has begun to show presence as a comprehensive and hypothesis-free test. It can not only detect MTB without isolating specific pathogens but also suggest the co-infection pathogens or underlying tumor simultaneously, which is of benefit to assist in comprehensive clinical diagnosis. It also shows the potential to detect multiple drug resistance sites for precise treatment. However, considering the cost performance compared with conventional assays (especially Xpert MTB/RIF), mNGS seems to be overqualified for patients with mild and typical symptoms. Technology optimization of sequencing and analyzing should be conducted to improve the positive rate and broaden the applicable fields.
PubMed: 35433724
DOI: 10.3389/fmed.2022.802719