Topic Editors

Department of Biological Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401, USA
Dr. Ming-Liang He
Department of Biological Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong

Advanced Technologies for Drug Delivery, Pathogen Detection and Diagnostics

Abstract submission deadline
closed (30 April 2023)
Manuscript submission deadline
closed (30 June 2023)
Viewed by
35098

Topic Information

Dear Colleagues,

We are delighted to announce a call for submissions to a Topic of “Advanced Technologies for Drug Delivery, Pathogen Detection and Diagnostics”. The global pandemic has drawn increasing research attention on the development of advanced tools and technologies for molecular detection of pathogenic microorganisms, rapid diagnosis, and efficient drug delivery systems on infectious diseases. Close collaboration from researchers with expertise on chemical engineering, material technology, nanotechnology, pharmacology, molecular biology, immunology, and bioinformatics is highly desired. Taking this opportunity of organizing a topic collection, we would like to highlight innovative researches in related areas, in the scope from novel drug delivery systems for pathogenic microorganisms, nanovaccine development, host-pathogen interactions, evasion of RNA virus from innate immunity, to rapid, affordable and sensitive methods for pathogen detection and quantification. Your article can be written to focus on a specific research topic (Article format) by you and your group, or alternatively it can be written in the style of a Review of relevance to the community. We hope that this special collection would serve as an international platform for further interdisciplinary research discussion and cooperation, promoting the development of interdisciplinary research fields.

Dr. Xi Yao
Dr. Yung-Fu Chang
Dr. Ming-Liang He
Topic Editors

Keywords

  • nanomedicine
  • targeted delivery
  • nanoparticles
  • micro/nanoneedle
  • antiviral
  • immunity
  • outer-membrane vehicle
  • exosome

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomedicines
biomedicines
4.7 3.7 2013 15.4 Days CHF 2600
Diagnostics
diagnostics
3.6 3.6 2011 20.7 Days CHF 2600
Journal of Nanotheranostics
jnt
- - 2020 26.8 Days CHF 1000
Micro
micro
- - 2021 22.5 Days CHF 1000
Pharmaceutics
pharmaceutics
5.4 6.9 2009 14.2 Days CHF 2900

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Published Papers (12 papers)

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14 pages, 1442 KiB  
Communication
Paving Way for a Paradigm Shift in Oncology: Curing Cancer by Loving It?
by Vuk Uskoković
Micro 2023, 3(3), 749-762; https://doi.org/10.3390/micro3030053 - 21 Sep 2023
Viewed by 743
Abstract
Plateaus in the efficacy of traditional methods for the treatment of cancer reached in the last decades call for the exploration of alternative models as their potential clinical complements. Here, the classical view of cancer as a tissue that is to be eradicated [...] Read more.
Plateaus in the efficacy of traditional methods for the treatment of cancer reached in the last decades call for the exploration of alternative models as their potential clinical complements. Here, the classical view of cancer as a tissue that is to be eradicated by methods describable by a compendium of militaristic metaphors is being challenged with a provocative idea: what if cancer can be cured with love condensed down to the level of molecular and cell biology? Correspondingly, the idea that love mimics the traits of the objects of its affection and helps them grow was translated to the level of cell biology by incorporating anti-apoptotic properties in healthy cells and promoting tumorigenesis in cancerous cells. Both the indirect and direct co-culture of the two cell types demonstrated hindered growth of cancer cells relative to that of their primary counterparts when these cellular modifications inspired by love for cancer were being implemented. The two experimental models reported here are emphasized as crude and simplistic methods derived from the idea that cancer may be best treated by being loved at the cellular and molecular biology levels. More comprehensive and effective methods may emanate from continued exploration and expansion of the intriguing and innovative avenue for cancer management proposed here. Full article
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12 pages, 2449 KiB  
Article
Pressure-Driven Sample Flow through an Electrospun Membrane Increases the Analyte Adsorption
by Aitsana Maslakova, Kirill Prusakov, Anastasia Sidorova, Elizaveta Pavlova, Alla Ramonova and Dmitry Bagrov
Micro 2023, 3(2), 566-577; https://doi.org/10.3390/micro3020038 - 26 May 2023
Cited by 1 | Viewed by 1718
Abstract
Electrospun polymer membranes are regarded as prospective biosensor components due to their large specific surface area and diverse opportunities for chemical modifications. However, their intricate porous structure can impede diffusion and render some analyte-binding sites inaccessible. To overcome these diffusion limitations and improve [...] Read more.
Electrospun polymer membranes are regarded as prospective biosensor components due to their large specific surface area and diverse opportunities for chemical modifications. However, their intricate porous structure can impede diffusion and render some analyte-binding sites inaccessible. To overcome these diffusion limitations and improve analyte adsorption onto the polymer, a pressure-driven sample flow through the membrane can be employed. To date, the efficiency of pressure-driven analyte delivery into these membranes has not been quantified. Here, we compare forced flow and passive sample diffusion through poly(dioxanone) electrospun membranes. We examine two model analytes, BSA and interleukin-1 beta (IL1b), to address both non-specific and specific binding. Following exposure of the membranes to the test solutions, we measured the residual concentrations of the analytes using fluorometry and enzyme-linked immunosorbent assay (ELISA) techniques. The pressure-driven sample loading was superior to passive diffusion, with a 2.8–11.5-fold change for physical adsorption and a 2.4–3.4-fold difference for specific binding. Our data can be useful for the development of immunoassays and microfluidic devices. Full article
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30 pages, 6701 KiB  
Review
Self-Assembled Monolayers Derived from Positively Charged Adsorbates on Plasmonic Substrates for MicroRNA Delivery: A Review
by Johnson Hoang, Pooria Tajalli, Mina Omidiyan, Maria D. Marquez, Orawan Khantamat, Wirote Tuntiwechapikul, Chien-Hung Li, Arati Kohlhatkar, Hung-Vu Tran, Preethi H. Gunaratne and T. Randall Lee
J. Nanotheranostics 2023, 4(2), 171-200; https://doi.org/10.3390/jnt4020009 - 08 May 2023
Cited by 2 | Viewed by 2642
Abstract
MicroRNA (miRNA) has emerged as a promising alternative therapeutic treatment for cancer, but its delivery has been hindered by low cellular uptake and degradation during circulation. In this review, we discuss the various methods of delivering miRNA, including viral and non-viral delivery systems [...] Read more.
MicroRNA (miRNA) has emerged as a promising alternative therapeutic treatment for cancer, but its delivery has been hindered by low cellular uptake and degradation during circulation. In this review, we discuss the various methods of delivering miRNA, including viral and non-viral delivery systems such as liposomes and nanoparticles. We also examine the use of nanoparticles for miRNA-based diagnostics. We focus specifically on non-viral delivery systems utilizing coinage metals in the form of nanoparticles and the use of self-assembled monolayers (SAMs) as a method of surface modification. We review the use of SAMs for the conjugation and delivery of small noncoding ribonucleic acid (ncRNA), particularly SAMs derived from positively charged adsorbates to generate charged surfaces that can interact electrostatically with negatively charged miRNA. We also discuss the effects of the cellular uptake of gold and other plasmonic nanoparticles, as well as the challenges associated with the degradation of oligonucleotides. Our review highlights the potential of SAM-based systems as versatile and robust tools for delivering miRNA and other RNAs in vitro and in vivo and the need for further research to address the challenges associated with miRNA delivery and diagnostics. Full article
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26 pages, 3743 KiB  
Review
Microneedles: An Emerging Vaccine Delivery Tool and a Prospective Solution to the Challenges of SARS-CoV-2 Mass Vaccination
by Ya-Xiu Feng, Huan Hu, Yu-Yuen Wong, Xi Yao and Ming-Liang He
Pharmaceutics 2023, 15(5), 1349; https://doi.org/10.3390/pharmaceutics15051349 - 27 Apr 2023
Cited by 4 | Viewed by 3335
Abstract
Vaccination is an effective measure to prevent infectious diseases. Protective immunity is induced when the immune system is exposed to a vaccine formulation with appropriate immunogenicity. However, traditional injection vaccination is always accompanied by fear and severe pain. As an emerging vaccine delivery [...] Read more.
Vaccination is an effective measure to prevent infectious diseases. Protective immunity is induced when the immune system is exposed to a vaccine formulation with appropriate immunogenicity. However, traditional injection vaccination is always accompanied by fear and severe pain. As an emerging vaccine delivery tool, microneedles overcome the problems associated with routine needle vaccination, which can effectively deliver vaccines rich in antigen-presenting cells (APCs) to the epidermis and dermis painlessly, inducing a strong immune response. In addition, microneedles have the advantages of avoiding cold chain storage and have the flexibility of self-operation, which can solve the logistics and delivery obstacles of vaccines, covering the vaccination of the special population more easily and conveniently. Examples include people in rural areas with restricted vaccine storage facilities and medical professionals, elderly and disabled people with limited mobility, infants and young children afraid of pain. Currently, in the late stage of fighting against COVID-19, the main task is to increase the coverage of vaccines, especially for special populations. To address this challenge, microneedle-based vaccines have great potential to increase global vaccination rates and save many lives. This review describes the current progress of microneedles as a vaccine delivery system and its prospects in achieving mass vaccination against SARS-CoV-2. Full article
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23 pages, 8399 KiB  
Review
Technegas, A Universal Technique for Lung Imaging in Nuclear Medicine: Technology, Physicochemical Properties, and Clinical Applications
by Isra Khatib and Paul M. Young
Pharmaceutics 2023, 15(4), 1108; https://doi.org/10.3390/pharmaceutics15041108 - 30 Mar 2023
Viewed by 3692
Abstract
Technegas was developed in Australia as an imaging radioaerosol in the late 1980s and is now commercialized by Cyclomedica, Pty Ltd. for diagnosing pulmonary embolism (PE). Technegas is produced by heating technetium-99m in a carbon crucible for a few seconds at high temperatures [...] Read more.
Technegas was developed in Australia as an imaging radioaerosol in the late 1980s and is now commercialized by Cyclomedica, Pty Ltd. for diagnosing pulmonary embolism (PE). Technegas is produced by heating technetium-99m in a carbon crucible for a few seconds at high temperatures (2750 °C) to generate technetium–carbon nanoparticles with a gas-like behaviour. The submicron particulates formed allow easy diffusion to the lung periphery when inhaled. Technegas has been used for diagnosis in over 4.4 m patients across 60 countries and now offers exciting opportunities in areas outside of PE, including asthma and chronic obstructive pulmonary disease (COPD). The Technegas generation process and the physicochemical attributes of the aerosol have been studied over the past 30 years in parallel with the advancement in different analytical methodologies. Thus, it is now well established that the Technegas aerosol has a radioactivity aerodynamic diameter of <500 nm and is composed of agglomerated nanoparticles. With a plethora of literature studying different aspects of Technegas, this review focuses on a historical evaluation of the different methodologies’ findings over the years that provides insight into a scientific consensus of this technology. Also, we briefly discuss recent clinical innovations using Technegas and a brief history of Technegas patents. Full article
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23 pages, 6689 KiB  
Article
Transferrin-Grafted Albumin Nanoparticles for the Targeted Delivery of Apocynin and Neuroprotection in an In Vitro Model of the BBB
by Venkatesan Perumal, Arun Reddy Ravula, Agnieszka Agas, Manisha Kannan, Xiangshan Liu, Shanmuga Sundari I, Sivakumar Vijayaraghavalu, James Haorah, Yuanwei Zhang and Namas Chandra
Micro 2023, 3(1), 84-106; https://doi.org/10.3390/micro3010008 - 23 Jan 2023
Cited by 1 | Viewed by 2298
Abstract
Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide, affecting over 10 million people annually, with an estimated cost of $76.5 billion. Although apocynin freely transverses the blood–brain barrier (BBB), its application is limited due to its rapid elimination, [...] Read more.
Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide, affecting over 10 million people annually, with an estimated cost of $76.5 billion. Although apocynin freely transverses the blood–brain barrier (BBB), its application is limited due to its rapid elimination, low terminal half-life (t1/2 = 6.7 min), narrow dose–response relationship, and cytotoxicity, thereby requiring repeated dosages. With this study, we aimed to develop transferrin-functionalized nanoparticles encapsulating apocynin to treat neuroinflammation for targeted drug delivery to sites of brain injury. As a preliminary approach, we endeavored to optimize the formulation parameters of apocynin-loaded albumin nanoparticles prepared through the desolvation method. The nanoparticles were characterized for their size, polydispersity, surface charge, drug loading and in vitro drug release. In this study, we also investigated the anti-inflammatory and neuroprotective effects of free apocynin and nanoparticle-loaded apocynin in neuronal cells. We show that the developed formulation displayed monodispersed, nanosized particles with higher entrapment efficiency, loading, stability, and sustained release profiles. The permeability of the nanoparticles across HBMECs reached the maximum at 67%. The in vivo evaluation revealed the enhanced uptake of transferrin-anchored nanoparticles in the brain tissues when compared with unmodified nanoparticles after I.V. administration. In vivo nanoparticle localization studies using a blast TBI (bTBI) model and confocal fluorescence microscopy have shown that tf-apoANPs are successful in delivering relatively high amounts of nanoparticles to the brain parenchyma and glial cells compared to non-targeted nanoparticles. We also establish that targeted nanoparticles accumulate in the brain. In conclusion, tf-apoANPs are efficacious carriers for targeted delivery across the blood–brain barrier to potentially treat neuroinflammation in brain injury and other diseases. Full article
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21 pages, 3442 KiB  
Article
Classification of Systemic Lupus Erythematosus Using Raman Spectroscopy of Blood and Automated Computational Detection Methods: A Novel Tool for Future Diagnostic Testing
by Emma L. Callery, Camilo L. M. Morais, Lucy Nugent and Anthony W. Rowbottom
Diagnostics 2022, 12(12), 3158; https://doi.org/10.3390/diagnostics12123158 - 14 Dec 2022
Cited by 2 | Viewed by 1713
Abstract
The aim of this study was to explore the proof of concept for using Raman spectroscopy as a diagnostic platform in the setting of systemic lupus erythematosus (SLE). We sought to identify unique Raman signatures in serum blood samples to successfully segregate SLE [...] Read more.
The aim of this study was to explore the proof of concept for using Raman spectroscopy as a diagnostic platform in the setting of systemic lupus erythematosus (SLE). We sought to identify unique Raman signatures in serum blood samples to successfully segregate SLE patients from healthy controls (HC). In addition, a retrospective audit was undertaken to assess the clinical utility of current testing platforms used to detect anti-double stranded DNA (dsDNA) antibodies (n = 600). We examined 234 Raman spectra to investigate key variances between SLE patients (n = 8) and HC (n = 4). Multi-variant analysis and classification model construction was achieved using principal component analysis (PCA), PCA-linear discriminant analysis and partial least squares-discriminant analysis (PLS-DA). We achieved the successful segregation of Raman spectra from SLE patients and healthy controls (p-value < 0.0001). Classification models built using PLS-DA demonstrated outstanding performance characteristics with 99% accuracy, 100% sensitivity and 99% specificity. Twelve statistically significant (p-value < 0.001) wavenumbers were identified as potential diagnostic spectral markers. Molecular assignments related to proteins and DNA demonstrated significant Raman intensity changes between SLE and HC groups. These wavenumbers may serve as future biomarkers and offer further insight into the pathogenesis of SLE. Our audit confirmed previously reported inconsistencies between two key methodologies used to detect anti-dsDNA, highlighting the need for improved laboratory testing for SLE. Raman spectroscopy has demonstrated powerful performance characteristics in this proof-of-concept study, setting the foundations for future translation into the clinical setting. Full article
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17 pages, 5608 KiB  
Article
Methylene Blue Delivery Mediated by Focused Ultrasound-Induced Blood–Brain Barrier Disruption Reduces Neural Damage and Amyloid-Beta Plaques by AQP-4 Upregulation
by Hyo Jin Choi, Mun Han, Byeongjin Jung, Yu-Ri Hong, Seulgi Shin, Sungsu Lim, Eun-Hee Lee, Yun Kyung Kim and Juyoung Park
Biomedicines 2022, 10(12), 3191; https://doi.org/10.3390/biomedicines10123191 - 08 Dec 2022
Cited by 3 | Viewed by 2375
Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, causing progressive cognitive decline, memory impairment, and neurological deficits. Methylene blue (MB), an antioxidant, has emerged as a potential drug for the treatment of AD owing to its cognitive improvement and neuroprotective functions. [...] Read more.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, causing progressive cognitive decline, memory impairment, and neurological deficits. Methylene blue (MB), an antioxidant, has emerged as a potential drug for the treatment of AD owing to its cognitive improvement and neuroprotective functions. Despite the small molecular size of MB, which can cross the BBB, the therapeutic effective dosage using a BBB-permeable delivery system in a specific brain localization remains unclear. In this study, we presented magnetic resonance–guided focused ultrasound (MRgFUS) as a delivery system to enhance BBB permeability for the effective treatment of AD. MRgFUS using two ultrasound intensities (0.25 and 0.32 MPa) was used to intravenously deliver MB to the hippocampal region. Compared with treatment with 0.25 MPa FUS, treatment with 0.32 MPa FUS significantly enhanced MB brain accumulation. Deposition of amyloid-β (Aβ) plaques and neural cell damage was significantly reduced in 0.32 MPa FUS/MB-treated APP/PS1 mice. Furthermore, aquaporin-4 expression increased significantly in the 0.32 MPa FUS and 0.32 MPa FUS/MB groups without glial fibrillary acidic protein activation. The results from this study demonstrate that FUS improved MB delivery to the brain, and FUS/MB combination treatment reduced the number of Aβ plaques. This study revealed the potential of FUS-BBBD as an effective strategy to enhance the efficacy of therapeutic drugs for AD. Full article
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18 pages, 1225 KiB  
Review
Acne Vulgaris, Atopic Dermatitis and Rosacea: The Role of the Skin Microbiota—A Review
by Giorgia Condrò, Marta Guerini, Michela Castello and Paola Perugini
Biomedicines 2022, 10(10), 2523; https://doi.org/10.3390/biomedicines10102523 - 09 Oct 2022
Cited by 12 | Viewed by 6231
Abstract
The skin harbors a huge number of different microorganisms such as bacteria, fungi and viruses, and it acts as a protective shield to prevent the invasion of pathogens and to maintain the health of the commensal microbiota. Several studies, in fact, have shown [...] Read more.
The skin harbors a huge number of different microorganisms such as bacteria, fungi and viruses, and it acts as a protective shield to prevent the invasion of pathogens and to maintain the health of the commensal microbiota. Several studies, in fact, have shown the importance of the skin microbiota for healthy skin. However, this balance can be altered by intrinsic and extrinsic factors, leading to the development of skin disease, such as acne vulgaris (AV), atopic dermatitis (AD) and rosacea(RS). Although these diseases are widespread and affect both adolescents and adults, the scientific correlation between these disorders and the skin microbiota and physiological parameters (TEWL, hydration and lipid composition) is still unclear. This review aims to investigate the current literature regarding the correlation between the skin microbiota and its imbalance underlying microbiological aspects, how the skin microbiota changes over the course of the disease and the current possible treatments. The following reported studies show a general imbalance of the bacterial flora. For this reason, more in-depth studies are necessary to explore the different subspecies and strains involved in all three diseases. Full article
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15 pages, 1530 KiB  
Article
Development of a Novel Lipid-Based Nanosystem Functionalized with WGA for Enhanced Intracellular Drug Delivery
by Gabriela Hädrich, Gustavo Richter Vaz, Juliana Bidone, Virginia Campello Yurgel, Helder Ferreira Teixeira, Alexandre Gonçalves Dal Bó, Luciano da Silva Pinto, Mariana Appel Hort, Daniela Fernandes Ramos, Antonio Sergio Varela Junior, Pedro Eduardo Almeida da Silva and Cristiana Lima Dora
Pharmaceutics 2022, 14(10), 2022; https://doi.org/10.3390/pharmaceutics14102022 - 23 Sep 2022
Cited by 1 | Viewed by 1993
Abstract
Despite a considerable number of new antibiotics under going clinical trials, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The use of lipid nanocarriers provides several advantages such as protection from compound degradation, increased bioavailability, and controlled and targeted drug release. [...] Read more.
Despite a considerable number of new antibiotics under going clinical trials, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The use of lipid nanocarriers provides several advantages such as protection from compound degradation, increased bioavailability, and controlled and targeted drug release. Wheat germ agglutinin (WGA) is known to have its receptors on the alveolar epithelium and increase phagocytosis. The present study aimed to produce nanostructured lipid carriers with novel glycosylated amphiphilic employed to attach WGA on the surface of the nanocarriers to improve intracellular drug delivery. High-pressure homogenization was employed to prepare the lipid nanocarriers. In vitro, high-content analysis and flow cytometry assay was employed to study the increased uptake by macrophages when the nanocarriers were grafted with WGA. A lipid nanocarrier with surface-functionalized WGA protein (~200 nm, PDI > 0.3) was successfully produced and characterized. The system was loaded with a lipophilic model compound (quercetin; QU), demonstrating the ability to encapsulate a high amount of compound and release it in a controlled manner. The nanocarrier surface functionalization with the WGA protein increased the phagocytosis by macrophages. The system proposed here has characteristics to be further explored to treat intracellular pathogens. Full article
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25 pages, 5079 KiB  
Review
Supramolecular Adhesive Materials with Antimicrobial Activity for Emerging Biomedical Applications
by Changshun Hou, Yung-Fu Chang and Xi Yao
Pharmaceutics 2022, 14(8), 1616; https://doi.org/10.3390/pharmaceutics14081616 - 02 Aug 2022
Cited by 3 | Viewed by 3368
Abstract
Traditional adhesives or glues such as cyanoacrylates, fibrin glue, polyethylene glycol, and their derivatives have been widely used in biomedical fields. However, they still suffer from numerous limitations, including the mechanical mismatch with biological tissues, weak adhesion on wet surfaces, biological incompatibility, and [...] Read more.
Traditional adhesives or glues such as cyanoacrylates, fibrin glue, polyethylene glycol, and their derivatives have been widely used in biomedical fields. However, they still suffer from numerous limitations, including the mechanical mismatch with biological tissues, weak adhesion on wet surfaces, biological incompatibility, and incapability of integrating desired multifunction. In addition to adaptive mechanical and adhesion properties, adhesive biomaterials should be able to integrate multiple functions such as stimuli-responsiveness, control-releasing of small or macromolecular therapeutic molecules, hosting of various cells, and programmable degradation to fulfill the requirements in the specific biological systems. Therefore, rational molecular engineering and structural designs are required to facilitate the development of functional adhesive materials. This review summarizes and analyzes the current supramolecular design strategies of representative adhesive materials, serving as a general guide for researchers seeking to develop novel adhesive materials for biomedical applications. Full article
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10 pages, 905 KiB  
Article
Diagnostic Yield of Xpert MTB/RIF Assay Using Bronchoalveolar Lavage Fluid in Detecting Mycobacterium tuberculosis among the Sputum-Scarce Suspected Pulmonary TB Patients
by Mohammad Khaja Mafij Uddin, Md. Fahim Ather, Sharmin Akter, Rumana Nasrin, Tanjina Rahman, Sk Nazmul Kabir, S. M. Mazidur Rahman, Stephane Pouzol, Jonathan Hoffmann and Sayera Banu
Diagnostics 2022, 12(7), 1676; https://doi.org/10.3390/diagnostics12071676 - 10 Jul 2022
Cited by 4 | Viewed by 2440
Abstract
Tuberculosis (TB) remains one of the leading causes of death worldwide and is caused by the single infectious agent Mycobacterium tuberculosis (Mtb). Although sputum is the most common specimen for pulmonary TB detection, some other respiratory specimens, such as bronchoalveolar lavage (BAL) fluid, [...] Read more.
Tuberculosis (TB) remains one of the leading causes of death worldwide and is caused by the single infectious agent Mycobacterium tuberculosis (Mtb). Although sputum is the most common specimen for pulmonary TB detection, some other respiratory specimens, such as bronchoalveolar lavage (BAL) fluid, gastric lavage (GL), and induced sputum (IS), are also collected from patients who are unable to deliver sputum. In this study, we aimed to evaluate the diagnostic performances of different test methods for TB diagnosis using BAL fluid specimens from sputum-scarce pulmonary TB patients. In this current study, a total of 210 BAL fluid specimens were collected and subjected to culture on Lowenstein–Jensen (L-J) medium, using an N-acetyl-L-cysteine-Sodium Hydroxide decontamination and digestion method, Xpert MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) assay, and acid-fast bacilli (AFB) microscopy with a Ziehl–Neelsen staining method for the detection of pulmonary TB. The sensitivity and specificity of these methods were then analyzed against the composite reference standard (CRS). Additionally, the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of these assays. Among the 210 specimens, 39 (18.6%), 27 (12.8%), and 12 (5.7%) were found positive with Xpert assay, culture, and AFB microscopy, respectively. Considering the CRS, 42 (20%) were positive as the final diagnosis. The Xpert assay had a significantly higher sensitivity (92.9%, 95% CI: 80.5–98.5) compared to culture (64.3%, 95% CI: 48.0–78.4) and AFB microscopy (28.6%, 95% CI: 15.7–44.6) against the CRS. Additionally, the area under the ROC curve (AUC) for the Xpert assay, culture, and AFB microscopy accounted for 0.964, 0.821, and 0.655, respectively, when using CRS as the reference. In conclusion, our study findings demonstrated that the Xpert assay conferred a considerable diagnostic potential compared to other conventional methods for the diagnosis of pulmonary TB from BAL fluid specimens. Full article
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