Expert Review of Molecular Diagnostics最新文献

Introduction: SARS-CoV-2, seasonal influenza, and respiratory syncytial virus (RSV) are major causes of acute respiratory infections in all age groups and responsible for an enormous socio-economic burden. The recently coined term 'tripledemic' describes co-circulation of these three viruses, a novel epidemiological paradigm that poses profound public health implications.

Areas covered: Real-time reverse transcription polymerase chain reaction (RT-PCR) is now considered the reference method for the diagnosis of SARS-CoV-2, influenza, and RSV infections. Syndromic-based multiplex RT-PCR panels that simultaneously detect several respiratory viruses have become increasingly common. This review explores available molecular diagnostics (MDx) platforms for the diagnosis of SARS-CoV-2, influenza, and RSV in the same biological sample. Within some limitations of the published validation and diagnostic accuracy studies, both laboratory-based and point-of-care multiplex panels proved highly performant in identifying SARS-CoV-2, influenza A, influenza B, and RSV. Improved operational efficiency and faster turnaround times make these assays potentially cost-effective or even cost-saving.

Expert opinion: The adoption of multiplex MDx assays for the contemporary detection of SARS-CoV-2, influenza, RSV, and other respiratory pathogens will likely increase in the next few years. To maximize the clinical usefulness and cost-effectiveness of these assays, locally issued guidelines and protocols on their implementation should be adopted.

Introduction: Distinguishing bacterial from viral infections remains a challenge due to clinically indistinguishable presentations. Non-infectious conditions such as malignancy, pulmonary emboli and rheumatological conditions may also present with fever. Consequently, patients are often over-treated with antimicrobial agents or may not receive adequate therapy.

Areas covered: This article provides a comprehensive review of a novel protein host-signature assay, the MeMed BV assay, that distinguishes bacterial from viral infections. The focus is on the use of the test in respiratory tract infections including assay performance characteristics, clinical profiles and data on cost-effectiveness. The changing landscape from the use of single inflammatory biomarkers, such as C-reactive protein, to alternative and diverse host signature biomarkers, is also discussed.

Expert opinion: The MeMed BV assay is one of several novel host biomarkers that provide rapid results and demonstrate enhanced performance compared to single test biomarkers. This assay has been validated by a large number of carefully controlled clinical trials that demonstrate improved performance characteristics for distinguishing bacterial infections or combined bacterial/viral infections from viral or noninfectious causes of fever compared to C-reactive protein and procalcitonin. However, these trials may over-state assay performance as samples with equivocal band results are often not included in the statistical analysis. More real-world studies addressing clinical implementation of the MeMed BV assay or other biomarkers into ambulatory settings are needed.

Introduction: Digital human immunodeficiency virus self-testing (HIVST) leverages digital supports, enhancing accessibility, privacy, and early detection of HIV, empowering individuals to manage their HIV status and facilitating timely linkage to care. These advancements contribute to reduced HIV transmission and thereby lead to improved health outcomes.

Areas covered: This perspective examines the current landscape of digital HIVST strategies, highlighting challenges that must be addressed and opportunities that are presented as the field evolves.

Expert opinion: Implementing advances in digital HIVST requires a unified digital network architecture that integrates proven tools (digital supports) within the World Health Organization's One Health Agenda. This includes strategies effective in diverse settings, supported by evolving governance and ethics frameworks that ensure data safety and privacy. Although data on linkages to care are strong, digital HIVST strategies may need further field validation, especially in low-income countries. Key challenges include systems integration, data privacy safeguards, and implementation of proven digital supports. Embracing digital readers, machine learning solutions, chatbots, and wearable solutions can improve outcomes that translate to significant public health benefits in the context of HIV elimination. Investing in digital technologies and integrating digital HIVST into HIV prevention and care programs can enable progress toward UNAIDS elimination targets.

Introduction: Liquid biopsy is an innovative advancement in oncology, offering a noninvasive method for early cancer detection and monitoring by analyzing circulating tumor cells, DNA, RNA, and other biomarkers in bodily fluids. This technique has the potential to revolutionize precision oncology by providing real-time analysis of tumor dynamics, enabling early detection, monitoring treatment responses, and tailoring personalized therapies based on the molecular profiles of individual patients.

Areas covered: In this review, the authors discuss current methodologies, technological challenges, and clinical applications of liquid biopsy. This includes advancements in detecting minimal residual disease, tracking tumor evolution, and combining liquid biopsy with other diagnostic modalities for precision oncology. Key areas explored are the sensitivity, specificity, and integration of multi-omics, AI, ML, and LLM technologies.

Expert opinion: Liquid biopsy holds great potential to revolutionize cancer care through early detection and personalized treatment strategies. However, its success depends on overcoming technological and clinical hurdles, such as ensuring high sensitivity and specificity, interpreting results amidst tumor heterogeneity, and making tests accessible and affordable. Continued innovation and collaboration are crucial to fully realize the potential of liquid biopsy in improving early cancer detection, treatment, and monitoring.

Introduction: There have been many recent advancements in the treatment of bladder cancer including the approval of novel intravesical agents for non-muscle-invasive disease and systemic-targeted therapeutics for muscle-invasive and advanced disease. However, treatment strategies for bladder cancer are still largely based on clinicopathologic characteristics.

Areas covered: Based on primary literature sourced from PubMed, Embase, and Cochrane Library, we review the current status of molecular markers and biomarker panels with respective to their value in predicting response to standard chemotherapeutics and novel agents in non-muscle-invasive, muscle-invasive, and advanced bladder cancer.

Expert opinion: Several biomarkers based on molecular characterization of tumors and quantification of circulating tumor DNA have been associated with response or resistance to standard chemotherapeutics. More recent investigations have reported on predictive biomarkers for novel therapeutics in bladder cancer, although large-scale validation is still needed. Given the increasing therapeutic options for this disease, employment of such predictive biomarkers may help guide treatment selection and sequencing.

Introduction: While Pneumocystis pneumonia (PcP) remains a major AIDS-defining disease, the majority of cases of PcP now present in the HIV-negative cohort, causing significant mortality. PcP PCR diagnosis is not novel, and the optimal route of diagnosis remains unclear, with an imperfect reference method and complexity in result interpretation for alternative tests.

Areas covered: This extensive review utilizing a literature search underpinning a recent systematic review/meta-analysis discusses the technical and clinical performance of PcP PCR, the added benefits of PCR testing, future aspects/considerations, and how PCR may be best used in clinical algorithms to provide a probability of PcP.

Expert opinion: Given the current imperfect reference test for PcP, an alternative would be beneficial. Concerns over PcP PCR generating false positive results are valid but can be resolved by using positivity thresholds that drive specificity. Unfortunately, the extensive range of PCR assays complicates the provision of a PCR reference method. Combination testing incorporating PCR and B-D-Glucan, along with clinical and host risk factors, is key to understanding the individual probability of PcP. It is critical that access to PcP PCR testing is improved through technical and logistical development. Conversely, syndromic approaches including PcP need to be fully evaluated.

Introduction: Approximately 15 million deaths occur globally each year due to infectious diseases. Timely diagnosis is crucial in promoting cure and preventing disease transmission. Currently, molecular diagnostics have replaced many conventional diagnostic tools due to their inherent limitations. However, the full potential of Immuno Polymerase Chain Reaction (IPCR) remains largely untapped.

Areas covered: This review focuses on the use of IPCR in the diagnosis of different bacterial diseases, highlighting its advantages over traditional methods.

Expert opinion: Early and accurate diagnosis of infectious diseases is crucial because it enhances treatment effectiveness, reduces morbidity and mortality, helps identify potential causes of sepsis earlier, and reduces the risk of unknowingly spreading the disease to others. IPCR in turn has shown promise for the early diagnosis of bacterial diseases as an alternative to conventional culture-based or serological diagnostic assays leading to delayed diagnosis and treatment. IPCR has the potential to revolutionize the diagnostic field due to its increased sensitivity and specificity. Although efforts are needed to reduce the time of the assay and to reduce background noise, IPCR can be combined with other platforms like lateral flow assay/biosensors/automation to improve its use as a point-of-care assay, especially in resource-limited settings.