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Guliy OI, Evstigneeva SS, Khanadeev VA, Dykman LA. Antibody Phage Display Technology for Sensor-Based Virus Detection: Current Status and Future Prospects. BIOSENSORS 2023; 13:640. [PMID: 37367005 DOI: 10.3390/bios13060640] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/31/2023] [Accepted: 06/08/2023] [Indexed: 06/28/2023]
Abstract
Viruses are widespread in the environment, and many of them are major pathogens of serious plant, animal, and human diseases. The risk of pathogenicity, together with the capacity for constant mutation, emphasizes the need for measures to rapidly detect viruses. The need for highly sensitive bioanalytical methods to diagnose and monitor socially significant viral diseases has increased in the past few years. This is due, on the one hand, to the increased incidence of viral diseases in general (including the unprecedented spread of a new coronavirus infection, SARS-CoV-2), and, on the other hand, to the need to overcome the limitations of modern biomedical diagnostic methods. Phage display technology antibodies as nano-bio-engineered macromolecules can be used for sensor-based virus detection. This review analyzes the commonly used virus detection methods and approaches and shows the prospects for the use of antibodies prepared by phage display technology as sensing elements for sensor-based virus detection.
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Affiliation(s)
- Olga I Guliy
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Subdivision of the Federal State Budgetary Research Institution Saratov Federal Scientific Centre of the Russian Academy of Sciences (IBPPM RAS), 13 Prospect Entuziastov, Saratov 410049, Russia
| | - Stella S Evstigneeva
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Subdivision of the Federal State Budgetary Research Institution Saratov Federal Scientific Centre of the Russian Academy of Sciences (IBPPM RAS), 13 Prospect Entuziastov, Saratov 410049, Russia
| | - Vitaly A Khanadeev
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Subdivision of the Federal State Budgetary Research Institution Saratov Federal Scientific Centre of the Russian Academy of Sciences (IBPPM RAS), 13 Prospect Entuziastov, Saratov 410049, Russia
| | - Lev A Dykman
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Subdivision of the Federal State Budgetary Research Institution Saratov Federal Scientific Centre of the Russian Academy of Sciences (IBPPM RAS), 13 Prospect Entuziastov, Saratov 410049, Russia
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2
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Babaei A, Pouremamali A, Rafiee N, Sohrabi H, Mokhtarzadeh A, de la Guardia M. Genosensors as an alternative diagnostic sensing approaches for specific detection of various certain viruses: a review of common techniques and outcomes. Trends Analyt Chem 2022; 155:116686. [PMID: 35611316 PMCID: PMC9119280 DOI: 10.1016/j.trac.2022.116686] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 05/08/2022] [Accepted: 05/15/2022] [Indexed: 12/19/2022]
Abstract
Viral infections are responsible for the deaths of millions of people throughout the world. Since outbreak of highly contagious and mutant viruses such as contemporary sars-cov-2 pandemic, has challenged the conventional diagnostic methods, the entity of a thoroughly sensitive, specific, rapid and inexpensive detecting technique with minimum level of false-positivity or -negativity, is desperately needed more than any time in the past decades. Biosensors as minimized devices could detect viruses in simple formats. So far, various nucleic acid, immune- and protein-based biosensors were designed and tested for recognizing the genome, antigen, or protein level of viruses, respectively; however, nucleic acid-based sensing techniques, which is the foundation of constructing genosensors, are preferred not only because of their ultra-sensitivity and applicability in the early stages of infections but also for their ability to differentiate various strains of the same virus. To date, the review articles related to genosensors are just confined to particular pathogenic diseases; In this regard, the present review covers comprehensive information of the research progress of the electrochemical, optical, and surface plasmon resonance (SPR) genosensors that applied for human viruses' diseases detection and also provides a well description of viruses' clinical importance, the conventional diagnosis approaches of viruses and their disadvantages. This review would address the limitations in the current developments as well as the future challenges involved in the successful construction of sensing approaches with the functionalized nanomaterials and also allow exploring into core-research works regarding this area.
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Affiliation(s)
- Abouzar Babaei
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Amir Pouremamali
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Nastaran Rafiee
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hessamaddin Sohrabi
- Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Miguel de la Guardia
- Department of Analytical Chemistry, University of Valencia, Dr. Moliner 50, 46100, Burjassot, Valencia, Spain
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3
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Long S. In pursuit of sensitivity: Lessons learned from viral nucleic acid detection and quantification on the Raindance ddPCR platform. Methods 2022; 201:82-95. [PMID: 33839286 PMCID: PMC8501152 DOI: 10.1016/j.ymeth.2021.04.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/27/2021] [Accepted: 04/06/2021] [Indexed: 12/11/2022] Open
Abstract
Sensitive PCR detection of viral nucleic acids plays a critical role in infectious disease research, diagnosis and monitoring. In the context of SARS-CoV-2 detection, recent reports indicate that digital PCR-based tests are significantly more sensitive than traditional qPCR tests. Numerous factors can influence digital PCR reaction sensitivity. In this review, using a model for human HIV infection and the Raindance ddPCR platform as an example, we describe technical aspects that contribute to sensitive viral signal detection in DNA and RNA from tissue samples, which often harbor viral reservoirs and serve as better predictors of disease outcome and indicators of treatment efficacy.
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Affiliation(s)
- Samuel Long
- AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States.
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4
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Guliy OI, Zaitsev BD, Semyonov AP, Karavaeva OA, Fomin AS, Staroverov SA, Burov AM, Borodina IA. Sensor System Based on a Piezoelectric Resonator with a Lateral Electric Field for Virus Diagnostics. ULTRASOUND IN MEDICINE & BIOLOGY 2022; 48:901-911. [PMID: 35232607 DOI: 10.1016/j.ultrasmedbio.2022.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 01/20/2022] [Accepted: 01/21/2022] [Indexed: 06/14/2023]
Abstract
A sensor system based on a piezoelectric resonator with a lateral electric field in the frequency range 6-7 MHz of the electric field for virus detection is described. Through use of the transmissible virus causing gastroenteritis in pigs and specific antibodies, the possibility of detecting the virus in suspension in real time was determined. It was found that the frequency dependence of the real and imaginary parts of the electrical impedance of such a resonator loaded with a virus suspension changes significantly after the addition of specific antibodies to the suspension. No changes are observed if the antibodies are not specific. Thus, the results obtained illustrate the possibility of detecting viruses in situ, directly in the liquid phase, if the change in the real or imaginary parts of the electrical impedance after the addition of antibodies is used as an analytical signal. The possibility of virus detection in the presence of foreign viral particles has been illustrated.
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Affiliation(s)
- Olga I Guliy
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Saratov Scientific Center of the Russian Academy of Sciences, Saratov, Russia.
| | - Boris D Zaitsev
- Kotel'nikov Institute of Radio Engineering and Electronics of RAS, Saratov, Russia
| | - Alexander P Semyonov
- Kotel'nikov Institute of Radio Engineering and Electronics of RAS, Saratov, Russia
| | - Olga A Karavaeva
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Saratov Scientific Center of the Russian Academy of Sciences, Saratov, Russia
| | - Alexander S Fomin
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Saratov Scientific Center of the Russian Academy of Sciences, Saratov, Russia
| | - Sergey A Staroverov
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Saratov Scientific Center of the Russian Academy of Sciences, Saratov, Russia
| | - Andrey M Burov
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Saratov Scientific Center of the Russian Academy of Sciences, Saratov, Russia
| | - Irina A Borodina
- Kotel'nikov Institute of Radio Engineering and Electronics of RAS, Saratov, Russia
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5
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Islam MT, Alam ARU, Sakib N, Hasan MS, Chakrovarty T, Tawyabur M, Islam OK, Al-Emran HM, Jahid MIK, Anwar Hossain M. A rapid and cost-effective multiplex ARMS-PCR method for the simultaneous genotyping of the circulating SARS-CoV-2 phylogenetic clades. J Med Virol 2021; 93:2962-2970. [PMID: 33491822 DOI: 10.1101/2020.10.08.20209692] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 01/15/2021] [Accepted: 01/20/2021] [Indexed: 05/23/2023]
Abstract
Tracing the globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) phylogenetic clades by high-throughput sequencing is costly, time-consuming, and labor-intensive. We here propose a rapid, simple, and cost-effective amplification refractory mutation system (ARMS)-based multiplex reverse-transcription polymerase chain reaction (PCR) assay to identify six distinct phylogenetic clades: S, L, V, G, GH, and GR. Our multiplex PCR is designed in a mutually exclusive way to identify V-S and G-GH-GR clade variants separately. The pentaplex assay included all five variants and the quadruplex comprised of the triplex variants alongside either V or S clade mutations that created two separate subsets. The procedure was optimized with 0.2-0.6 µM primer concentration, 56-60°C annealing temperature, and 3-5 ng/µl complementary DNA to validate on 24 COVID-19-positive samples. Targeted Sanger sequencing further confirmed the presence of the clade-featured mutations with another set of primers. This multiplex ARMS-PCR assay is a fast, low-cost alternative and convenient to discriminate the circulating phylogenetic clades of SARS-CoV-2.
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Affiliation(s)
- Mohammad Tanvir Islam
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Asm Rubayet Ul Alam
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Najmuj Sakib
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Mohammad Shazid Hasan
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Tanay Chakrovarty
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Mohammad Tawyabur
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Ovinu Kibria Islam
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Hassan M Al-Emran
- Department of Biomedical Engineering, Jashore University of Science and Technology, Jashore, Bangladesh
| | | | - Mohammad Anwar Hossain
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
- Department of Microbiology, University of Dhaka, Dhaka, Bangladesh
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6
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Park CE. Diagnostic Methods of Respiratory Virus Infections and Infection Control. KOREAN JOURNAL OF CLINICAL LABORATORY SCIENCE 2021. [DOI: 10.15324/kjcls.2021.53.1.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Chang-Eun Park
- Department of Biomedical Laboratory Science, Molecular Diagnostics Research Institute, Namseoul University, Cheonan, Korea
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7
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Long S, Berkemeier B. Development of a reverse transcription droplet digital PCR (RT-ddPCR) assay for sensitive detection of simian immunodeficiency virus (SIV). Virol J 2021; 18:35. [PMID: 33588884 PMCID: PMC7883996 DOI: 10.1186/s12985-021-01503-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 02/01/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Simian immunodeficiency virus (SIV)-infected rhesus macaques constitute an excellent model of human HIV infection. Sensitive detection of SIV RNA in cell and tissue samples from infected animals subjected to treatment regimens becomes especially critical in determining which therapeutic attempts are successful, and consequently, which interventions should be prioritized in HIV cure research. RESULTS In this report, we describe the design and testing of a Raindance ddPCR platform-based, sensitive SIV reverse transcription droplet digital PCR (RT-ddPCR) assay by exploring the combinations of various priming conditions and reverse transcriptases, and testing one-step vs. two-step procedures, to eliminate background signal(s) and enable detection and quantification of low level target signals. CONCLUSIONS Similar reaction conditions and assay validation procedures can be explored for potential development of additional assays for other applications that require sensitive detection of low-level targets in RNA samples.
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Affiliation(s)
- Samuel Long
- AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
| | - Brian Berkemeier
- AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA
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8
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Islam MT, Alam ARU, Sakib N, Hasan MS, Chakrovarty T, Tawyabur M, Islam OK, Al-Emran HM, Jahid MIK, Anwar Hossain M. A rapid and cost-effective multiplex ARMS-PCR method for the simultaneous genotyping of the circulating SARS-CoV-2 phylogenetic clades. J Med Virol 2021; 93:2962-2970. [PMID: 33491822 PMCID: PMC8014803 DOI: 10.1002/jmv.26818] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 01/15/2021] [Accepted: 01/20/2021] [Indexed: 01/09/2023]
Abstract
Tracing the globally circulating severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) phylogenetic clades by high‐throughput sequencing is costly, time‐consuming, and labor‐intensive. We here propose a rapid, simple, and cost‐effective amplification refractory mutation system (ARMS)‐based multiplex reverse‐transcription polymerase chain reaction (PCR) assay to identify six distinct phylogenetic clades: S, L, V, G, GH, and GR. Our multiplex PCR is designed in a mutually exclusive way to identify V–S and G–GH–GR clade variants separately. The pentaplex assay included all five variants and the quadruplex comprised of the triplex variants alongside either V or S clade mutations that created two separate subsets. The procedure was optimized with 0.2–0.6 µM primer concentration, 56–60°C annealing temperature, and 3–5 ng/µl complementary DNA to validate on 24 COVID‐19‐positive samples. Targeted Sanger sequencing further confirmed the presence of the clade‐featured mutations with another set of primers. This multiplex ARMS‐PCR assay is a fast, low‐cost alternative and convenient to discriminate the circulating phylogenetic clades of SARS‐CoV‐2.
Multiplex ARMS‐PCR (amplification refractory mutation system‐polymerase chain reaction) method for genotyping major severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 clades). Identify the mutated region of circulating phylogenetically SARS‐CoV‐2 clades. PCR conditions were optimized and validated to identify V–S and G–GH–GR clade.
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Affiliation(s)
- Mohammad Tanvir Islam
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Asm Rubayet Ul Alam
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Najmuj Sakib
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Mohammad Shazid Hasan
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Tanay Chakrovarty
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Mohammad Tawyabur
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Ovinu Kibria Islam
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Hassan M Al-Emran
- Department of Biomedical Engineering, Jashore University of Science and Technology, Jashore, Bangladesh
| | | | - Mohammad Anwar Hossain
- Department of Microbiology, Jashore University of Science and Technology, Jashore, Bangladesh.,Department of Microbiology, University of Dhaka, Dhaka, Bangladesh
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Shirin T, Bhuiyan TR, Charles RC, Amin S, Bhuiyan I, Kawser Z, Rahat A, Alam AN, Sultana S, Aleem MA, Khan MH, Khan SR, LaRocque RC, Calderwood SB, Ryan ET, Slater DM, Banu S, Clemens J, Harris JB, Flora MS, Qadri F. Antibody responses after COVID-19 infection in patients who are mildly symptomatic or asymptomatic in Bangladesh. Int J Infect Dis 2020; 101:220-225. [PMID: 33031941 PMCID: PMC7534791 DOI: 10.1016/j.ijid.2020.09.1484] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/29/2020] [Accepted: 09/30/2020] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES Studies on serological responses following coronavirus disease-2019 (COVID-19) have been published primarily in individuals who are moderately or severely symptomatic, but there are few data from individuals who are mildly symptomatic or asymptomatic. METHODS We measured IgG, IgM, and IgA to the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using enzyme-linked immunosorbent assay in mildly symptomatic (n = 108) and asymptomatic (n = 63) on days 1, 7, 14, and 30 following RT-PCR confirmation in Bangladesh and when compared with pre-pandemic samples, including healthy controls (n = 73) and individuals infected with other viruses (n = 79). RESULTS Mildly symptomatic individuals developed IgM and IgA responses by day 14 in 72% and 83% of individuals, respectively, while 95% of individuals developed IgG response, and rose to 100% by day 30. In contrast, individuals infected with SARS-CoV-2 but who remained asymptomatic developed antibody responses significantly less frequently, with only 20% positive for IgA and 22% positive for IgM by day 14, and 45% positive for IgG by day 30 after infection. CONCLUSIONS These results confirm immune responses are generated following COVID-19 who develop mildly symptomatic illness. However, those with asymptomatic infection do not respond or have lower antibody levels. These results will impact modeling needed for determining herd immunity generated by natural infection or vaccination.
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Affiliation(s)
- Tahmina Shirin
- Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | | | - Richelle C Charles
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Shaheena Amin
- Infectious Diseases Division, icddr,b, Mohakhali, Dhaka, Bangladesh
| | - Imran Bhuiyan
- Institute for Developing Science & Health Initiatives (ideSHi), Dhaka, Bangladesh
| | - Zannat Kawser
- Institute for Developing Science & Health Initiatives (ideSHi), Dhaka, Bangladesh
| | - Asifuzaman Rahat
- Institute for Developing Science & Health Initiatives (ideSHi), Dhaka, Bangladesh
| | - Ahmed Nawsher Alam
- Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | - Sharmin Sultana
- Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | - Md Abdul Aleem
- Infectious Diseases Division, icddr,b, Mohakhali, Dhaka, Bangladesh
| | | | | | - Regina C LaRocque
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Stephen B Calderwood
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Edward T Ryan
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Damien M Slater
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
| | - Sayera Banu
- Infectious Diseases Division, icddr,b, Mohakhali, Dhaka, Bangladesh
| | - John Clemens
- Infectious Diseases Division, icddr,b, Mohakhali, Dhaka, Bangladesh
| | - Jason B Harris
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA, USA
| | | | - Firdausi Qadri
- Infectious Diseases Division, icddr,b, Mohakhali, Dhaka, Bangladesh.
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10
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Parhizkar Roudsari P, Alavi-Moghadam S, Payab M, Sayahpour FA, Aghayan HR, Goodarzi P, Mohamadi-jahani F, Larijani B, Arjmand B. Auxiliary role of mesenchymal stem cells as regenerative medicine soldiers to attenuate inflammatory processes of severe acute respiratory infections caused by COVID-19. Cell Tissue Bank 2020; 21:405-425. [PMID: 32588163 PMCID: PMC7315014 DOI: 10.1007/s10561-020-09842-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 06/13/2020] [Indexed: 02/07/2023]
Abstract
Acute respiratory infections as one of the most common problems of healthcare systems also can be considered as an important reason for worldwide morbidity and mortality from infectious diseases. Coronaviruses are a group of well-known respiratory viruses that can cause acute respiratory infections. At the current state, the 2019 novel coronavirus is cited as the most worldwide problematic agent for the respiratory system. According to investigations, people with old age and underlying diseases are at higher risk of 2019 novel coronavirus infection. Indeed, they may show a severe form of the disease (with severe acute respiratory infections). Based on the promising role of cell therapy and regenerative medicine approaches in the treatment of several life-threatening diseases, it seems that applying cell-based approaches can also be a hopeful strategy for improving subjects with severe acute respiratory infections caused by the 2019 novel coronavirus. Herein, due to the amazing effects of mesenchymal stem cells in the treatment of various diseases, this review focuses on the auxiliary role of mesenchymal stem cells to reduce inflammatory processes of acute respiratory infections caused by the 2019 novel coronavirus.
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Affiliation(s)
- Peyvand Parhizkar Roudsari
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moloud Payab
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Forough Azam Sayahpour
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Hamid Reza Aghayan
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Goodarzi
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fereshteh Mohamadi-jahani
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Arjmand
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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11
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Arden KE, Greer RM, Wang CYT, Mackay IM. Genotypic diversity, circulation patterns and co-detections among rhinoviruses in Queensland, 2001. Access Microbiol 2019; 2:acmi000075. [PMID: 33062934 PMCID: PMC7525053 DOI: 10.1099/acmi.0.000075] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 10/07/2019] [Indexed: 12/13/2022] Open
Abstract
Purpose Rhinoviruses (RVs) occur more frequently than other viruses and more often in people displaying symptoms than in those without. We sought to estimate the spectrum of RV diversity, RV species seasonality and to analyse RV involvement in respiratory virus co-detections. Methodology A convenience collection of 1179 airway sample extracts from patients with suspected respiratory infections, collected during 2001, was subjected to comprehensive molecular testing. Results RVs were the most common virus detected. We were able to genotype ~90 % of RV detections, identifying 70 distinct RVs, spanning all three species. RV-Bs were under-represented. We found RV species co-circulated at times, although one species usually dominated. Each species displayed a bimodal distribution. Conclusion Notably, RVs and influenza A viruses (IFAV) seldom co-occurred, supporting their roles as primary pathogens of the airway among acutely ill infants. Whether RV circulation has a moderating or controlling effect on the IFAV season or is controlled by it cannot be determined from these data. Despite the frequent perception that RVs commonly co-occur with another virus, our findings indicated this was not always the case. Nearly 80 % of RV detections occurred alone. Understanding more about population-level interference between viruses may allow us to harness aspects of it to generate a non-specific antiviral intervention that mimics a putative protective effect. For routine respiratory virus screening to best serve the patient, RV testing should be a principal component of any acute respiratory illness testing algorithm throughout the year.
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Affiliation(s)
- Katherine E Arden
- Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia
| | - Ristan M Greer
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Claire Y T Wang
- Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia.,Centre for Children's Health Research, Children's Health Queensland South Brisbane, Queensland, 4101, Australia
| | - Ian M Mackay
- Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia
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12
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Lee YJ, Kim HB, Kim BS, Kim CK, Kim CH, Kim HY, Kim S, Kim Y, Park C, Seo JH, Sol IS, Sung M, Song MS, Song DJ, Ahn YM, Oh HL, Yu J, Lee KS, Lee E, Lee JS, Jang GC, Jang YY, Chung EH, Chung HL, Choi SM, Choi YJ, Han MY, Yang HJ, Shim JY, Kim JT. Seasonal patterns and etiologies of croup in children during the period 2010–2015: A multicenter retrospective study. ALLERGY ASTHMA & RESPIRATORY DISEASE 2019. [DOI: 10.4168/aard.2019.7.2.78] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Affiliation(s)
- Yong Ju Lee
- Department of Pediatrics, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
| | - Hyo-Bin Kim
- Department of Pediatrics, Asthma and Allergy Center, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Bong-Seong Kim
- Department of Pediatrics, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Chang-Keun Kim
- Department of Pediatrics, Asthma and Allergy Center, Inje University Sanggye Paik Hospital, Seoul, Korea
| | - Cheol Hong Kim
- Department of Pediatrics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Hyung Young Kim
- Department of Pediatrics, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Sangyoung Kim
- SCH Biomedical Informatics Research Unit, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Yunsun Kim
- SCH Biomedical Informatics Research Unit, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Chorong Park
- SCH Biomedical Informatics Research Unit, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Ju-Hee Seo
- Department of Pediatrics, Dankook University Hospital, Cheonan, Korea
| | - In Suk Sol
- Department of Pediatrics, Yonsei University Severance Hospital, Seoul, Korea
| | - Myongsoon Sung
- Department of Pediatrics, Soonchunhyang University Gumi Hospital, Gumi, Korea
| | - Min Seob Song
- Department of Pediatrics, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Dae Jin Song
- Department of Pediatrics, Korea University Guro Hospital, Seoul, Korea
| | - Young Min Ahn
- Department of Pediatrics, Eulji University Eulji General Hospital, Seoul, Korea
| | - Hea Lin Oh
- Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea
| | - Jinho Yu
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung Suk Lee
- Department of Pediatrics, Hanyang University Guri Hospital, Guri, Korea
| | - Eun Lee
- Department of Pediatrics, Chonnam National University Hospital, Gwangju, Korea
| | - Ju Suk Lee
- Department of Pediatrics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Gwang Cheon Jang
- Department of Pediatrics, National Health Insurance Service, Ilsan Hospital, Ilsan, Korea
| | - Yoon Young Jang
- Department of Pediatrics, Daegu Catholic University Medical Center, Daegu, Korea
| | - Eun Hee Chung
- Department of Pediatrics, Chungnam National University Hospital, Daejeon, Korea
| | - Hai Lee Chung
- Department of Pediatrics, Daegu Catholic University Medical Center, Daegu, Korea
| | - Sung-Min Choi
- Department of Pediatrics, Dongguk University Gyungju Hospital, Gyungju, Korea
| | - Yun Jung Choi
- Department of Pediatrics, Sowha Children's Hospital, Seoul, Korea
- Department of Pediatrics, Seoul National University Children Hospital, Seoul, Korea
| | - Man Yong Han
- Department of Pediatrics, CHA University CHA Bundang Medical Center, Seongnam, Korea
| | - Hyeon-Jong Yang
- SCH Biomedical Informatics Research Unit, Soonchunhyang University Seoul Hospital, Seoul, Korea
- Department of Pediatrics, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Jung Yeon Shim
- Division of Pediatric Allergy & Pulmonology, Department of Pediatrics, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea
| | - Jin-Tack Kim
- Department of Pediatric Allergy & Pneumology, Catholic University Uijeongbu St. Mary's Hospital, Uijeongbu, Korea
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13
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Law N, Kumar D. Post-transplant Viral Respiratory Infections in the Older Patient: Epidemiology, Diagnosis, and Management. Drugs Aging 2018; 34:743-754. [PMID: 28965331 PMCID: PMC7100819 DOI: 10.1007/s40266-017-0491-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Organ and stem cell transplantation has been one of the greatest advances in modern medicine, and is the primary treatment modality for many end-stage diseases. As our population ages, so do the transplant recipients, and with that comes many new challenges. Respiratory viruses have been a large contributor to the mortality and morbidity of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Respiratory viruses are generally a long-term complication of transplantation and primarily acquired in the community. With the emergence of molecular methods, newer respiratory viruses are being detected. Respiratory viruses appear to cause severe disease in the older transplant population. Influenza vaccine remains the mainstay of prevention in transplant recipients, although immunogenicity of current vaccines is suboptimal. Limited therapies are available for other respiratory viruses. The next decade will likely bring newer antivirals and vaccines to the forefront. Our goal is to provide the most up to date knowledge of respiratory viral infections in our aging transplant population.
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Affiliation(s)
- Nancy Law
- Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, PMB 11-174, 585 University Avenue, Toronto, ON, M5G 2N2, Canada
| | - Deepali Kumar
- Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, PMB 11-174, 585 University Avenue, Toronto, ON, M5G 2N2, Canada.
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Gregianini TS, Seadi CF, Menegolla I, Martins LG, Ikuta N, Wolf JM, Lunge VR. Human metapneumovirus in Southern Brazil. Rev Soc Bras Med Trop 2018. [DOI: 10.1590/0037-8682-0435-2017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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15
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A Mathematical Model for the Macrophage Response to Respiratory Viral Infection in Normal and Asthmatic Conditions. Bull Math Biol 2017; 79:1979-1998. [PMID: 28741104 DOI: 10.1007/s11538-017-0315-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Accepted: 06/30/2017] [Indexed: 12/30/2022]
Abstract
Respiratory viral infections are common in the general population and one of the most important causes of asthma aggravation and exacerbation. Despite many studies, it is not well understood how viral infections cause more severe symptoms and exacerbations in asthmatics. We develop a mathematical model of two types of macrophages that play complementary roles in fighting viral infection: classically [Formula: see text]-[Formula: see text] and alternatively activated macrophages [Formula: see text]-[Formula: see text]. [Formula: see text]-[Formula: see text] destroy infected cells and tissues to remove viruses, while [Formula: see text]-[Formula: see text] repair damaged tissues. We show that a higher viral load or longer duration of infection provokes a stronger immune response from the macrophage system. By adjusting the parameters, we model the differences in response to respiratory viral infection in normal and asthmatic subjects and show how this skews the system toward a response that generates more severe symptoms in asthmatic patients.
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16
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Mai MV, Krauthammer M. Controlling testing volume for respiratory viruses using machine learning and text mining. AMIA ... ANNUAL SYMPOSIUM PROCEEDINGS. AMIA SYMPOSIUM 2017; 2016:1910-1919. [PMID: 28269950 PMCID: PMC5333257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Viral testing for pediatric inpatients with respiratory symptoms is common, with considerable associated charges. In an attempt to reduce testing volumes, we studied whether data available at the time of admission could aid in identifying children with low likelihood of having a particular viral origin of their symptoms, and thus safely forgo broad viral testing. We collected clinical data for 1,685 pediatric inpatients receiving respiratory virus testing from 2010-2012. Machine-learning on the data allowed us to construct pre-test models predicting whether a patient would test positive for a particular virus. Text mining improved the predictions for one viral test. Cost-sensitive models optimized for test sensitivity showed reasonable test specificities and an ability to reduce test volume by up to 46% for single viral tests. We conclude that diverse forms of data in the electronic medical record can be used productively to build models that help physicians reduce testing volumes.
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Affiliation(s)
- Mark V Mai
- The Children's Hospital of Philadelphia, Philadelphia, PA
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17
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Davido B, Badr C, Lagrange A, Makhloufi S, De Truchis P, Perronne C, Salomon J, Dinh A. Serum protein electrophoresis: an interesting diagnosis tool to distinguish viral from bacterial community-acquired pneumonia. Eur J Clin Microbiol Infect Dis 2016; 35:899-902. [PMID: 26936614 DOI: 10.1007/s10096-016-2613-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 02/16/2016] [Indexed: 11/26/2022]
Abstract
29-69 % of pneumonias are microbiologically documented because it can be considered as an invasive procedure with variable test sensitivity. However, it drastically impacts therapeutic strategy in particular the use of antibiotics. Serum protein electrophoresis (SPEP) is a routine and non-invasive test commonly used to identify serum protein disorders. As virus and bacteria may induce different globulins production, we hypothesize that SPEP can be used as an etiological diagnosis test. Retrospective study conducted from 1/1/13 until 5/1/15 among patient hospitalized for an acute community-acquired pneumonia based on fever, crackles and radiological abnormalities. α/β, α/γ, β/γ globulins and albumin/globulin (A/G) ratio were calculated from SPEP. Data were analyzed in 3 groups: documented viral (DVP) or bacterial pneumonia (DBP) and supposedly bacterial pneumonia (SBP). We used ANOVA statistic test with multiple comparisons using CI95 and ROC curve to compare them. 109 patients included divided into DBP (n = 16), DVP (n = 26) and SBP (n = 67). Mean age was 62 ± 18 year-old with a sex ratio M/F of 1.3. Underlying conditions (e.g. COPD, diabetes) were comparable between groups in multivariate analysis. Means of A/G ratio were 0.80 [0.76-0.84], 0.96 [0.91-1.01], 1.08 [0.99-1.16] respectively for DBP, SBP and DVP (p = 0.0002). A/G ratio cut-off value of 0.845 has a sensitivity of 87.5 % and a specificity of 73.1 %. A/G ratio seems to be an easy diagnostic tool to differentiate bacterial from viral pneumonia. A/G ratio cut-off value below 0.845 seems to be predictable of a bacterial origin and support the use of antibiotics.
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Affiliation(s)
- B Davido
- Maladies Infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France.
- Infectious Diseases Department, Raymond Poincaré Teaching Hospital, Garches, 92380, France.
| | - C Badr
- Maladies Infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France
| | - A Lagrange
- Maladies Infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France
| | - S Makhloufi
- Maladies Infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France
| | - P De Truchis
- Maladies Infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France
| | - C Perronne
- Maladies Infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France
| | - J Salomon
- Maladies Infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France
| | - A Dinh
- Maladies Infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France
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18
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Isaiah A, Pereira KD, Correa AG. Tracheal Infections. INFECTIOUS DISEASES IN PEDIATRIC OTOLARYNGOLOGY 2016. [PMCID: PMC7153446 DOI: 10.1007/978-3-319-21744-4_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Infectious processes of the trachea represent a distinct clinical entity with an evolving landscape owing to advances in airway management and vaccination practices. Untreated inflammatory processes of the trachea may present in the form of acute airway obstruction, potentially resulting in significant morbidity and even mortality. Therefore it is important to recognize the cardinal features of some of the common tracheal infectious processes to differentiate them from non-infectious pathology, as the latter is associated with a more indolent course. As with most other infectious processes of the airway, pathogens causing tracheal infection can be bacterial, viral or fungal in nature. Viral etiology represents the most common cause of laryngotracheal infection in a child. Bacterial infections of the trachea are responsible for more significant morbidity, including prolonged hospitalization, need for endotracheal intubation and even an occasional tracheostomy. The current chapter describes the clinical features and microbiology of tracheal infections at large, explores the utility of diagnostic tests, and provides an algorithm for management.
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19
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Pecchini R, Berezin EN, Souza MC, Vaz-de-Lima LDA, Sato N, Salgado M, Ueda M, Passos SD, Rangel R, Catebelota A. Parainfluenza virus as a cause of acute respiratory infection in hospitalized children. Braz J Infect Dis 2015; 19:358-62. [PMID: 25922290 PMCID: PMC9427530 DOI: 10.1016/j.bjid.2015.03.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2014] [Revised: 03/30/2015] [Accepted: 03/31/2015] [Indexed: 11/29/2022] Open
Abstract
Background Human parainfluenza viruses account for a significant proportion of lower respiratory tract infections in children. Objective To assess the prevalence of Human parainfluenza viruses as a cause of acute respiratory infection and to compare clinical data for this infection against those of the human respiratory syncytial virus. Methods A prospective study in children younger than five years with acute respiratory infection was conducted. Detection of respiratory viruses in nasopharyngeal aspirate samples was performed using the indirect immunofluorescence reaction. Length of hospital stay, age, clinical history and physical exam, clinical diagnoses, and evolution (admission to Intensive Care Unit or general ward, discharge or death) were assessed. Past personal (premature birth and cardiopathy) as well as family (smoking and atopy) medical factors were also assessed. Results A total of 585 patients were included with a median age of 7.9 months and median hospital stay of six days. No difference between the HRSV+ and HPIV+ groups was found in terms of age, gender or length of hospital stay. The HRSV+ group had more fever and cough. Need for admission to the Intensive Care Unit was similar for both groups but more deaths were recorded in the HPIV+ group. The occurrence of parainfluenza peaked during the autumn in the first two years of the study. Conclusion Parainfluenza was responsible for significant morbidity, proving to be the second-most prevalent viral agent in this population after respiratory syncytial virus. No difference in clinical presentation was found between the two groups, but mortality was higher in the HPIV+ group.
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Affiliation(s)
| | | | | | | | - Neuza Sato
- Center for Immunology, Instituto Adolfo Lutz, São Paulo, SP, Brazil
| | | | - Mirthes Ueda
- Center for Immunology, Instituto Adolfo Lutz, São Paulo, SP, Brazil
| | | | - Raphael Rangel
- Irmandade da Santa Casa de Misericórdia de São Paulo, SP, Brazil
| | - Ana Catebelota
- Irmandade da Santa Casa de Misericórdia de São Paulo, SP, Brazil
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20
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Tovey ER, Stelzer-Braid S, Toelle BG, Oliver BG, Reddel HK, Willenborg CM, Belessis Y, Garden FL, Jaffe A, Strachan R, Eyles D, Rawlinson WD, Marks GB. Rhinoviruses significantly affect day-to-day respiratory symptoms of children with asthma. J Allergy Clin Immunol 2015; 135:663-9.e12. [PMID: 25476729 PMCID: PMC7173323 DOI: 10.1016/j.jaci.2014.10.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Revised: 08/29/2014] [Accepted: 10/14/2014] [Indexed: 01/05/2023]
Abstract
BACKGROUND Viruses are frequently associated with acute exacerbations of asthma, but the extent to which they contribute to the level of day-to-day symptom control is less clear. OBJECTIVE We sought to explore the relationship between viral infections, host and environmental factors, and respiratory symptoms in children. METHODS Sixty-seven asthmatic children collected samples twice weekly for an average of 10 weeks. These included nasal wash fluid and exhaled breath for PCR-based detection of viral RNA, lung function measurements, and records of medication use and asthma and respiratory symptoms in the previous 3 days. Atopy, mite allergen exposure, and vitamin D levels were also measured. Mixed-model regression analyses were performed. RESULTS Human rhinoviruses (hRVs) were detected in 25.5% of 1232 nasal samples and 11.5% of breath samples. Non-hRV viruses were detected in less than 3% of samples. hRV in nasal samples was associated with asthma symptoms (cough and phlegm: odds ratio = 2.0; 95% CI = 1.4-2.86, P = .0001; wheeze and chest tightness: odds ratio = 2.34, 95% CI = 1.55-3.52, P < .0001) and with cold symptoms, as reported concurrently with sampling and 3 to 4 days later. No differences were found between the 3 hRV genotypes (hRV-A, hRV-B, and hRV-C) in symptom risk. A history of inhaled corticosteroid use, but not atopic status, mite allergen exposure, or vitamin D levels, modified the association between viruses and asthma symptoms. CONCLUSION The detection of nasal hRV was associated with a significantly increased risk of day-to-day asthma symptoms in children. Host, virus genotype, and environmental factors each had only a small or no effect on the relationship of viral infections to asthma symptoms.
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Affiliation(s)
- Euan R Tovey
- Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.
| | - Sacha Stelzer-Braid
- Virology Research Laboratory, SEALS, Prince of Wales Hospital, Sydney, Australia; School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Brett G Toelle
- Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; Sydney Local Health District, Sydney, Australia
| | - Brian G Oliver
- Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; University of Technology Sydney, Sydney, Australia
| | - Helen K Reddel
- Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia
| | | | - Yvonne Belessis
- School of Women's and Children's Health, University of New South Wales, Sydney, Australia; Sydney Children's Hospital, Sydney, Australia
| | - Frances L Garden
- Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; Ingham Institute of Applied Medical Research, New South Wales, Sydney, Australia; South Western Sydney Clinical School, University of New South Wales, Sydney, Australia
| | - Adam Jaffe
- School of Women's and Children's Health, University of New South Wales, Sydney, Australia; Sydney Children's Hospital, Sydney, Australia
| | | | - Darryl Eyles
- Queensland Brain Institute, University of Queensland, Brisbane, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Brisbane, Australia
| | - William D Rawlinson
- Virology Research Laboratory, SEALS, Prince of Wales Hospital, Sydney, Australia; Sydney Children's Hospital, Sydney, Australia
| | - Guy B Marks
- Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; South Western Sydney Clinical School, University of New South Wales, Sydney, Australia
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21
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Chen K, Jia R, Li L, Yang C, Shi Y. The aetiology of community associated pneumonia in children in Nanjing, China and aetiological patterns associated with age and season. BMC Public Health 2015; 15:113. [PMID: 25879996 PMCID: PMC4340102 DOI: 10.1186/s12889-015-1422-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Accepted: 01/15/2015] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Viral and atypical bacterial pathogens play an important role in respiratory tract infection. Using the Pneumoslide IgM test, the presented study explored the aetiology of community-acquired pneumonia and investigated further whether there was an association between age or season and aetiological organisms. METHODS Serum samples, taken between August 2011 and August 2013, from patients with CAP were tested with the Pneumoslide IgM kit. The Pneumoslide IgM technology can simultaneously diagnose 9 viral and atypical bacterial pathogens: Legionella pneumophila serogroup 1 (LP1), Mycoplasma pneumoniae (MP), Coxiella burnetii (COX), Chlamydophila pneumonia (CP), Adenovirus (ADV), Respiratory syncytial virus (RSV), Influenza A (INFA), Influenza B (INFB), Parainfluenza 1, 2 and 3 (PIVs). The data was analyzed by using Statistical Package for the Social Sciences for Windows (SPSS, version 11.0). RESULTS Of a total of 1204 serum samples tested, 624 samples were positive. M. pneumoniae was the dominant pathogen, with INFB, PIVs, and RSV ranking second to fourth, respectively. The positive percentages of MP, INFB, PIVs and RSV were found to be associated with age, especially MP, INFB and PIVs. The positive percentages of MP, PIVs and RSV were also found to be associated with season. The positive percentage of MP in autumn was the highest. The positive percentages of LP1 in August and September, ADV in June and INFB in March were relatively higher than that in other months. CONCLUSIONS The results show there were 4 main viral and atypical bacterial pathogens causing CAP in our study. Some pathogens were found to be associated with age and season. M. pneumoniae was the most predominant pathogen among these 9 pathogens. It is necessary to take preventative measures in order to prevent the spread of these pathogens in susceptible age groups during peak season.
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Affiliation(s)
- Keping Chen
- Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, Jiangsu, China.
| | - Runqing Jia
- College of Life Sciences and Bioengineering, Beijing University of Technology, 100 Ping Le Yuan, Beijing, 100022, China.
| | - Li Li
- Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, Jiangsu, China.
| | - Chuankun Yang
- Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, Jiangsu, China.
| | - Yan Shi
- Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, Jiangsu, China.
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22
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Wang M, Cai F, Wu X, Wu T, Su X, Shi Y. Incidence of viral infection detected by PCR and real-time PCR in childhood community-acquired pneumonia: a meta-analysis. Respirology 2015; 20:405-12. [PMID: 25615588 PMCID: PMC7169115 DOI: 10.1111/resp.12472] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Revised: 11/24/2014] [Accepted: 12/04/2014] [Indexed: 01/18/2023]
Abstract
Several studies examining the incidence of viral infection in childhood community‐acquired pneumonia (CAP) utilizing polymerase chain reaction (PCR) or real‐time PCR methods have been reported. We systematically searched Pubmed and Embase for studies reporting the incidence of respiratory viral infection in childhood CAP. The pooled incidences of viral infection were calculated with a random‐effects model. Sources of heterogeneity were explored by subgroup analysis and a univariant metaregression analysis. We included 21 eligible reports in our study. We found significant heterogeneity on the incidence of viral infection in childhood CAP. The random effects pooled incidence was 57.4% (95% confidence interval (CI): 50.8–64.1). The pooled incidence of mixed infection was 29.3% (95%CI: 23.0–35.6) with considerable heterogeneity. The pooled incidence of mixed infection was 29.3% (95%CI: 23.0–35.6). Rhinovirus, respiratory syncytial virus (RSV) and bocavirus were found to be the three most common viruses in childhood CAP. We also demonstrated that respiratory viruses were detected in 76.1% of patients aged ≤1 year, 63.1% of patients aged 2–5 years and 27.9% of patients aged ≥ 6 years. We conclude that respiratory viruses are widely detected in paediatric patients with CAP by PCR or real‐time PCR methods. More than half of viral infections are probably concurrent with bacterial infections. Rhinovirus, RSV and bocavirus are the three most frequent viruses identified in childhood CAP; the incidence of viral infection decreased with age.
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Affiliation(s)
- Min Wang
- Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
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23
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Taboada B, Espinoza MA, Isa P, Aponte FE, Arias-Ortiz MA, Monge-Martínez J, Rodríguez-Vázquez R, Díaz-Hernández F, Zárate-Vidal F, Wong-Chew RM, Firo-Reyes V, del Río-Almendárez CN, Gaitán-Meza J, Villaseñor-Sierra A, Martínez-Aguilar G, Salas-Mier MDC, Noyola DE, Pérez-Gónzalez LF, López S, Santos-Preciado JI, Arias CF. Is there still room for novel viral pathogens in pediatric respiratory tract infections? PLoS One 2014; 9:e113570. [PMID: 25412469 PMCID: PMC4239085 DOI: 10.1371/journal.pone.0113570] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Accepted: 10/24/2014] [Indexed: 11/30/2022] Open
Abstract
Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low.
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Affiliation(s)
- Blanca Taboada
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
| | - Marco A. Espinoza
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
| | - Pavel Isa
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
| | - Fernando E. Aponte
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
| | | | | | | | | | | | - Rosa María Wong-Chew
- Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., Mexico
| | | | | | - Jesús Gaitán-Meza
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Jalisco, Mexico
| | | | | | | | - Daniel E. Noyola
- Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
| | | | - Susana López
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
| | | | - Carlos F. Arias
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
- * E-mail:
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24
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Wurzel DF, Marchant JM, Yerkovich ST, Upham JW, Mackay IM, Masters IB, Chang AB. Prospective characterization of protracted bacterial bronchitis in children. Chest 2014; 145:1271-1278. [PMID: 24435356 PMCID: PMC7173205 DOI: 10.1378/chest.13-2442] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Prior studies on protracted bacterial bronchitis (PBB) in children have been retrospective or based on small cohorts. As PBB shares common features with other pediatric conditions, further characterization is needed to improve diagnostic accuracy among clinicians. In this study, we aim to further delineate the clinical and laboratory features of PBB in a larger cohort, with a specific focus on concurrent viral detection. METHODS Children with and without PBB (control subjects) undergoing flexible bronchoscopy were prospectively recruited. Basic immune function testing and lymphocyte subset analyses were performed. BAL specimens were processed for cellularity and microbiology. Viruses were identified using polymerase chain reaction (PCR) and bacteria were identified via culture. RESULTS The median age of the 104 children (69% male) with PBB was 19 months (interquartile range [IQR], 12-30 mo). Compared with control subjects, children with PBB were more likely to have attended childcare (OR, 8.43; 95% CI, 2.34-30.46). High rates of wheeze were present in both groups, and tracheobronchomalacia was common. Children with PBB had significantly elevated percentages of neutrophils in the lower airways compared with control subjects, and adenovirus was more likely to be detected in BAL specimens in those with PBB (OR, 6.69; 95% CI, 1.50-29.80). Median CD56 and CD16 natural killer (NK) cell levels in blood were elevated for age in children with PBB (0.7 × 109/L; IQR, 0.5-0.9 cells/L). CONCLUSIONS Children with PBB are, typically, very young boys with prolonged wet cough and parent-reported wheeze who have attended childcare. Coupled with elevated NK-cell levels, the association between adenovirus and PBB suggests a likely role of viruses in PBB pathogenesis.
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Affiliation(s)
- Danielle F Wurzel
- Queensland Children's Medical Research Institute, The University of Queensland, and Queensland Children's Respiratory Centre, Royal Children's Hospital, Brisbane, QLD.
| | - Julie M Marchant
- Queensland Children's Medical Research Institute, The University of Queensland, and Queensland Children's Respiratory Centre, Royal Children's Hospital, Brisbane, QLD
| | - Stephanie T Yerkovich
- School of Medicine, The University of Queensland, Brisbane, QLD; Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, QLD
| | - John W Upham
- School of Medicine, The University of Queensland, Brisbane, QLD; Department of Respiratory Medicine, Princess Alexandra Hospital, Brisbane, QLD
| | - Ian M Mackay
- Queensland Paediatric, Infectious Diseases Laboratory, Queensland Children's Medical Research Institute, Sir Albert, Sakzewski Virus Research Centre, Children's Health Queensland Hospital and Health Service, The University of Queensland, Herston, QLD
| | - I Brent Masters
- Queensland Children's Medical Research Institute, The University of Queensland, and Queensland Children's Respiratory Centre, Royal Children's Hospital, Brisbane, QLD
| | - Anne B Chang
- Queensland Children's Medical Research Institute, The University of Queensland, and Queensland Children's Respiratory Centre, Royal Children's Hospital, Brisbane, QLD; Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
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Baurakiades E, Costa VH, Raboni SM, de Almeida VRT, Larsen KSK, Kohler JN, Gozzo PDC, Klassen G, Manica GCM, de Noronha L. The roles of ADAM33, ADAM28, IL-13 and IL-4 in the development of lung injuries in children with lethal non-pandemic acute infectious pneumonia. J Clin Virol 2014; 61:585-9. [PMID: 25453333 DOI: 10.1016/j.jcv.2014.10.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Accepted: 10/11/2014] [Indexed: 11/16/2022]
Abstract
BACKGROUND ADAM28, ADAM33, IL-13, IL-4 and other cytokines (IL-6 and IL-10) seem to play important roles in the persistence and maintenance of acute inflammatory processes that ultimately lead to lung remodeling and pulmonary fibrosis, which may be responsible for the high morbidity and mortality rates associated with non-pandemic acute viral pneumonias in childhood. OBJECTIVES The aim of this study was to evaluate the roles of ADAM33, ADAM28, IL4, IL6, IL10 and IL13 in the development of inflammation and alveolar fibrosis due to lethal acute respiratory infections of the lower airway in a pediatric population, especially in those with viral etiology. STUDY DESIGN For this study, 193 cases were selected, and samples from the cases were processed for viral antigen detection by immunohistochemistry and then separated into two groups: virus-positive (n=68) and virus-negative (n=125). Immunohistochemistry was performed to assess the presence of metalloproteinases (ADAM33 and ADAM28) and inflammatory cytokines (IL-4, IL-13, IL-6, IL-10) in the alveolar septa. RESULTS The virus-positive group showed stronger immunolabeling for ADAM33, ADAM28, IL-4 and IL-13 (p<0.0001 for all variables). The staining intensities for ADAM33 and ADAM28 were directly proportional to the intensities for IL-4 and IL-13 (p<0.0001). CONCLUSIONS The results of this study suggest that these proteins play important roles in pulmonary inflammatory reactions elicited against etiological viral agents. In addition, these mediators may affect the process of lung remodeling and the development of pulmonary fibrosis.
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Affiliation(s)
- Emanuele Baurakiades
- Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil.
| | - Victor Horácio Costa
- Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil.
| | - Sonia Mara Raboni
- Hospital de Clínicas of Federal University of Paraná, Rua General Carneiro, 181, Centro, Curitiba, Paraná, Brazil.
| | | | - Kelly Susana Kunze Larsen
- Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil.
| | - Juliana Nemetz Kohler
- Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil.
| | - Priscilla do Carmo Gozzo
- Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil.
| | - Giseli Klassen
- Federal University of Paraná, Rua General Carneiro, 181, Centro, Curitiba, Paraná, Brazil.
| | - Graciele C M Manica
- Federal University of Paraná, Rua General Carneiro, 181, Centro, Curitiba, Paraná, Brazil.
| | - Lucia de Noronha
- Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil.
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Arango AE, Jaramillo S, Perez J, Ampuero JS, Espinal D, Donado J, Felices V, Garcia J, Laguna-Torres A. Influenza-like illness sentinel surveillance in one hospital in Medellin, Colombia. 2007-2012. Influenza Other Respir Viruses 2014; 9:1-13. [PMID: 25100179 PMCID: PMC4280811 DOI: 10.1111/irv.12271] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/09/2014] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND The city of Medellin in Colombia has almost no documentation of the causes of acute respiratory infections (ARIs). As part of an ongoing collaboration, we conducted an epidemiologic surveillance for influenza and other respiratory viruses. It described the influenza strains that were circulating in the region along with their distribution over time, and performing molecular characterization to some of those strains. This will contribute to the knowledge of local and national epidemiology. OBJECTIVES To analyze viral etiologic agents associated with influenza like illness (ILI) in participants reporting to one General hospital in Medelllin, Colombia. RESULTS From January 2007 to December 2012, a total of 2039 participants were enrolled. Among them, 1120 (54.9%) were male and 1364 (69%) were under the age of five. Only 124 (6%) were older than the age of 15. From all 2039 participants, 1040 samples were diagnosed by either isolation or RT-PCR. One or more respiratory viruses were found in 737 (36%) participants. Of those, 426 (57.8%) got influenza A or B. Adenoviral and parainfluenza infections represented 19.1% and 14.9% of viral infections, respectively. Influenza A was detected almost throughout the whole year except for the first quarter of 2010, right after the 2009 influenza A pandemic. Influenza B was detected in 2008, 2010, and 2012 with no pattern detected. During 2008 and 2010, both types circulated in about the same proportion. Unusually, in many months of 2012, the proportion of influenza B infections was higher than influenza A (ranging between 30% and 42%). The higher proportion of adenovirus was mainly detected in the last quarter of years 2007 and 2010. Adenoviral cases are more frequent in participants under the age of four. CONCLUSIONS The phylogenetic analysis of influenza viruses shows that only in the case of influenza A/H1N1, the circulating strains totally coincide with the vaccine strains each year.
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Affiliation(s)
- Ana Eugenia Arango
- Grupo Inmunovirología, Universidad de Antioquia, Medellín, Colombia; Sede de Investigación Universitaria (SIU) Torre 2 Lab. 532, Universidad de Antioquia, Medellín, Colombia
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de Souza Costa VH, Baurakiades E, Viola Azevedo ML, Traiano G, Kowal Rosales J, Kunze Larsen KS, Raboni SM, de Noronha L. Immunohistochemistry analysis of pulmonary infiltrates in necropsy samples of children with non-pandemic lethal respiratory infections (RSV; ADV; PIV1; PIV2; PIV3; FLU A; FLU B). J Clin Virol 2014; 61:211-5. [PMID: 25052332 PMCID: PMC7173026 DOI: 10.1016/j.jcv.2014.06.026] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Revised: 06/18/2014] [Accepted: 06/25/2014] [Indexed: 11/30/2022]
Abstract
Respiratory infections represent a globally cause of mortality in childhood. Individuals with impaired cellular immunity have more severe diseases. The inflammatory response appears to play role in recovery from these diseases. TCD8+ count (immunohistochemistry) was higher in the viral pneumonias (p
= 0.04). Tissue TCD8+ lymphocytes play role in the viral pneumonia inflammatory response. Background Acute viral respiratory infections represent a globally important cause of morbidity and mortality in childhood. An individual's cellular response appears to play a critical role in recovery from infections, given that individuals with impaired cellular immunity, congenital or acquired, have more severe diseases and secrete the virus for longer periods. Objectives The aim of this study was to immunohistochemically evaluate the expression of the cell surface antigens CD4, CD8, CD25, CD14 and CD74, in pneumonic infiltrates in the alveolar septa using paraffin-embedded lung samples from autopsies of immunocompetent children who died of lethal, non-pandemic, severe acute respiratory infections. Study design From 794 cases of pediatric autopsies of patients with severe respiratory disease (between 1960 and 2004), 193 cases were selected for this study. To identify subpopulations of inflammatory cells in the alveolar septa, cell surface antigen expression was assessed by immunohistochemistry using the following primary antibodies: anti-CD4, anti-CD8, anti-CD14, anti-CD25 and anti-CD74. Results The TCD8+ lymphocyte count was higher in the virus-positive group (p = 0.04) and was also much higher among cases that were positive for more than three viral types (p = 0.016). There were fewer CD14+ cells in cases of AdV (adenovirus) infection (p = 0.002), and there was a predominance of CD74+ cells in the histopathological pattern defined as interstitial pneumonitis (p = 0.037). Conclusions The results of this study demonstrate that TCD8+ lymphocytes present in the alveolar septa participate to a greater extent in the response toward viral pneumonia, while CD14+ cell numbers are often reduced in cases of AdV.
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Affiliation(s)
| | - Emanuele Baurakiades
- Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição, 1155 Prado Velho, Curitiba, Paraná, Brazil.
| | - Marina Louise Viola Azevedo
- Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição, 1155 Prado Velho, Curitiba, Paraná, Brazil.
| | - Gabriela Traiano
- Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição, 1155 Prado Velho, Curitiba, Paraná, Brazil.
| | - Jeana Kowal Rosales
- Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição, 1155 Prado Velho, Curitiba, Paraná, Brazil.
| | - Kelly Susana Kunze Larsen
- Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição, 1155 Prado Velho, Curitiba, Paraná, Brazil.
| | - Sonia Maria Raboni
- Universidade Federal do Paraná - Hospital de Clínicas, Rua General Carneiro, 181 Centro, Curitiba, Paraná, Brazil.
| | - Lucia de Noronha
- Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição, 1155 Prado Velho, Curitiba, Paraná, Brazil.
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Wurzel DF, Marchant JM, Clark JE, Masters IB, Yerkovich ST, Upham JW, Chang AB. Wet cough in children: infective and inflammatory characteristics in broncho-alveolar lavage fluid. Pediatr Pulmonol 2014; 49:561-8. [PMID: 23788413 DOI: 10.1002/ppul.22792] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2012] [Accepted: 02/11/2013] [Indexed: 01/26/2023]
Abstract
Wet cough is a common feature of many disease processes affecting children. Our aim was to examine the relationships between cough nature, lower airway infection (bacterial, viral, and viral-bacterial) and severity of neutrophilic airway inflammation. We hypothesized that viral-bacterial co-infection of the lower airway would be associated with wet cough and heightened neutrophilic airway inflammation. We prospectively recruited 232 children undergoing elective flexible bronchoscopy. Participants were grouped using a cough nature symptom-based approach, into wet, dry or no cough groups. Broncho-alveolar lavage (BAL) and clinical data, including presence, nature, and duration of cough and key demographic factors, were collected. Children with wet cough (n = 143) were more likely to have lower airway bacterial infection (OR 2.6, P = 0.001), viral infection (OR 2.04, P = 0.045) and viral-bacterial co-infection (OR 2.65, P = 0.042) compared to those without wet cough. Wet cough was associated with heightened airway neutrophilia (median 19%) as compared to dry or no cough. Viral-bacterial co-infection was associated with the highest median %neutrophils (33.5%) compared to bacteria only, virus/es only and no infection (20%, 18%, and 6%, respectively, P < 0.0001). Children with wet cough had higher rates of lower airway infection with bacteria and viruses. Maximal neutrophilic airway inflammation was seen in those with viral-bacterial co-infection. Cough nature may be a useful indicator of infection and inflammation of the lower airways in children.
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Affiliation(s)
- Danielle F Wurzel
- Queensland Children's Medical Research Institute, The University of Queensland, Royal Children's Hospital, Brisbane, Queensland, Australia; Queensland Children's Respiratory Centre, Royal Children's Hospital, Brisbane, Queensland, Australia
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Wurzel DF, Mackay IM, Marchant JM, Wang CYT, Yerkovich ST, Upham JW, Smith-Vaughan HC, Petsky HL, Chang AB. Adenovirus species C is associated with chronic suppurative lung diseases in children. Clin Infect Dis 2014; 59:34-40. [PMID: 24748519 PMCID: PMC4305137 DOI: 10.1093/cid/ciu225] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background. The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). Methods. Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV+). Presence of bacterial infection (defined as ≥104 colony-forming units/mL) was compared between BAL HAdV+ and HAdV negative (HAdV−) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. Results. Species C HAdVs were identified in 23 of 24 (96%) HAdV+ children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV+ BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38–7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV+. Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). Conclusions. HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV+ of the lower airways and influences the likelihood of bacterial coinfection.
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Affiliation(s)
- Danielle F Wurzel
- Queensland Children's Medical Research Institute, The University of Queensland Queensland Children's Respiratory Centre, Royal Children's Hospital
| | - Ian M Mackay
- Queensland Paediatric Infectious Diseases Laboratory, Queensland Children's Medical Research Institute, Sir Albert Sakzewski Virus Research Centre, Children's Health Queensland Hospital and Health Service, The University of Queensland, Herston
| | - Julie M Marchant
- Queensland Children's Medical Research Institute, The University of Queensland Queensland Children's Respiratory Centre, Royal Children's Hospital
| | - Claire Y T Wang
- Queensland Paediatric Infectious Diseases Laboratory, Queensland Children's Medical Research Institute, Sir Albert Sakzewski Virus Research Centre, Children's Health Queensland Hospital and Health Service, The University of Queensland, Herston
| | | | - John W Upham
- School of Medicine, The University of Queensland, Brisbane
| | - Heidi C Smith-Vaughan
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia
| | - Helen L Petsky
- Queensland Children's Respiratory Centre, Royal Children's Hospital Queensland Children's Medical Research Institute, Queensland University of Technology, Brisbane
| | - Anne B Chang
- Queensland Children's Respiratory Centre, Royal Children's Hospital Queensland Children's Medical Research Institute, Queensland University of Technology, Brisbane Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia
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Wurzel DF, Marchant JM, Clark JE, Mackay IM, Wang CYT, Sloots TP, Upham JW, Yerkovich ST, Masters IB, Baker PJ, Anderson-James S, Chang AB. Respiratory virus detection in nasopharyngeal aspirate versus bronchoalveolar lavage is dependent on virus type in children with chronic respiratory symptoms. J Clin Virol 2013; 58:683-8. [PMID: 24125830 PMCID: PMC7173340 DOI: 10.1016/j.jcv.2013.09.016] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Revised: 09/12/2013] [Accepted: 09/13/2013] [Indexed: 12/14/2022]
Abstract
Background The comparative yield of respiratory virus detection from nasopharyngeal aspirate (NPA) versus bronchoalveolar lavage (BAL) is uncertain. Furthermore, the significance of virus detection and its relationship to lower airway neutrophilic inflammation is poorly studied. Objectives To evaluate the sensitivity, specificity and predictive values of NPA for detecting respiratory viruses in BAL; and to determine the relationship between viruses and lower airway neutrophilia in children with non-acute respiratory illness. Study design 150 paired NPA and BAL samples were obtained from 75 children aged <18 years undergoing flexible bronchoscopy for investigation of chronic respiratory symptoms. Viral studies were performed using polymerase chain reaction (PCR). Cellularity studies were performed on BALs. Diagnostic parameters of NPA compared to BAL and associations between viruses and lower airway %neutrophils were evaluated. Results NPA had a higher yield than BAL for detection of any respiratory virus (52 versus 38, respectively). NPA had a high sensitivity (92%) and low specificity (57%) for detecting HRV in BAL with poor kappa agreement value of 0.398 (95% CI 0.218–0.578, p < 0.001). NPA had a fair sensitivity (69%) and good specificity (90.3%) for detecting HAdV on BAL, kappa agreement was 0.561 (95% CI 0.321–0.801, p < 0.001). HAdV positivity on NPA, compared to negativity, was independently associated with heightened airway neutrophilia [mean difference (95% CI): 18 (1,35); p = 0.042]. Conclusions NPA has a higher yield for respiratory virus detection than BAL, however its diagnostic accuracy is dependent on viral species. Adenovirus positivity is associated with significantly heightened lower airway neutrophilia in children with chronic respiratory symptoms.
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Affiliation(s)
- Danielle F Wurzel
- Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, Australia; Queensland Children's Respiratory Centre, Royal Children's Hospital, Brisbane, Australia.
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Vallières E, Renaud C. Clinical and economical impact of multiplex respiratory virus assays. Diagn Microbiol Infect Dis 2013; 76:255-61. [PMID: 23601453 PMCID: PMC7132665 DOI: 10.1016/j.diagmicrobio.2013.03.008] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Revised: 02/21/2013] [Accepted: 03/05/2013] [Indexed: 01/15/2023]
Abstract
During the last decade, a variety of molecular assays targeting respiratory viruses have been developed and commercialized. Therefore, multiplex PCR are increasingly used in everyday clinical practice. This improves our understanding of respiratory virus epidemiology and enhances our concerns about their clinical impact in specific patient populations. However, questions remain regarding cost-effectiveness of performing these diagnostic tests in routine and their real impact on patient care. This article will review available data and highlight unresolved questions about cost-effectiveness, infection control, clinical utility and public health impact of multiplex respiratory virus assays.
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Affiliation(s)
| | - Christian Renaud
- Département de Microbiologie et Immunologie, CHU Sainte-Justine, Université de Montréal, Montréal, Québec H3T 1C5, Canada
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Walia K. Point of care investigations in pediatric care to improve health care in rural areas. Indian J Pediatr 2013; 80:576-84. [PMID: 23564518 DOI: 10.1007/s12098-013-1016-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2012] [Accepted: 03/14/2013] [Indexed: 01/15/2023]
Abstract
The good quality laboratory services in developing countries are often limited to major urban centers. As a result, many commercially available high-quality diagnostic tests for infectious diseases are neither accessible nor affordable to patients in the rural areas. Health facilities in rural areas are compromised and this limits the usability and performance of the best medical diagnostic technologies in rural areas as they are designed for air-conditioned laboratories, refrigerated storage of chemicals, a constant supply of calibrators and reagents, stable electrical power, highly trained personnel and rapid transportation of samples. The advent of new technologies have allowed miniaturization and integration of complex functions, which has made it possible for sophisticated diagnostic tools to move out of the developed-world laboratory in the form of a "point of care"(POC) tests. Many diagnostic tests are being developed using these platforms. However, the challenge is to develop diagnostics which are inexpensive, rugged and well suited to the medical and social contexts of the developing world and do not compromise on accuracy and reliability. The already available POC tests which are reliable and affordable, like for HIV infection, malaria, syphilis, and some neglected tropical diseases, and POC tests being developed for other diseases if correctly used and effectively regulated after rigorous evaluation, have the potential to make a difference in clinical management and improve surveillance. In order to use these tests effectively they would need to be supported by technically competent manpower, availability of good-quality reagents, and healthcare providers who value and are able to interpret laboratory results to guide treatment; and a system for timely communication between the laboratory and the healthcare provider. Strengthening the laboratories at the rural level can enable utilization of these diagnostics for improving the diagnosis and management of infectious diseases among children which require prompt treatment and thus, considerably reduce morbidity and mortality among the pediatric age group.
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Affiliation(s)
- Kamini Walia
- Research and Development, PATH-India, A-9, Qutab Institutional Area, New Delhi 110016, India.
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Dolz S, Barragán E, Fuster Ó, Llop M, Cervera J, Such E, De Juan I, Palanca S, Murria R, Bolufer P, Luna I, Gómez I, López M, Ibáñez M, Sanz MA. Novel real-time polymerase chain reaction assay for simultaneous detection of recurrent fusion genes in acute myeloid leukemia. J Mol Diagn 2013; 15:678-86. [PMID: 23806810 DOI: 10.1016/j.jmoldx.2013.04.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2012] [Revised: 04/15/2013] [Accepted: 04/18/2013] [Indexed: 11/28/2022] Open
Abstract
The recent World Health Organization classification recognizes different subtypes of acute myeloid leukemia (AML) according to the presence of several recurrent genetic abnormalities. Detection of these abnormalities and other molecular changes is of increasing interest because it contributes to a refined diagnosis and prognostic assessment in AML and enables monitoring of minimal residual disease. These genetic abnormalities can be detected using single RT-PCR, although the screening is still labor intensive and costly. We have developed a novel real-time RT-PCR assay to simultaneously detect 15 AML-associated rearrangements that is a simple and easily applicable method for use in clinical diagnostic laboratories. This method showed 100% specificity and sensitivity (95% confidence interval, 91% to 100% and 92% to 100%, respectively). The procedure was validated in a series of 105 patients with AML. The method confirmed all translocations detected using standard cytogenetics and fluorescence in situ hybridization and some additional undetected rearrangements. Two patients demonstrated two molecular rearrangements simultaneously, with BCR-ABL1 implicated in both, in addition to RUNX1-MECOM in one patient and PML-RARA in another. In conclusion, this novel real-time RT-PCR assay for simultaneous detection of multiple AML-associated fusion genes is a versatile and sensitive method for reliable screening of recurrent rearrangements in AML.
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Affiliation(s)
- Sandra Dolz
- Laboratory of Molecular Biology, Department of Clinical Chemistry, University Hospital La Fe, Valencia, Spain
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Li L, Chen QY, Li YY, Wang YF, Yang ZF, Zhong NS. Comparison among nasopharyngeal swab, nasal wash, and oropharyngeal swab for respiratory virus detection in adults with acute pharyngitis. BMC Infect Dis 2013; 13:281. [PMID: 23786598 DOI: 10.1186/1471-2334-13-281] [citation(s)] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2013] [Accepted: 06/17/2013] [Indexed: 08/27/2024] Open
Abstract
BACKGROUND Acute pharyngitis is frequently seen in primary care. Acute viral pharyngitis may be easily misdiagnosed as acute bacterial pharyngitis. Laboratory-confirmed diagnosis of respiratory viruses is recommended. The purpose of this study was to compare the sensitivities among oropharyngeal swab (OPS), nasopharyngeal swab (NPS), and nasal wash (NW) in adults with acute pharyngitis. METHODS OPS, NPS, and NW were obtained from each participant with acute pharyngitis. The specimens were tested for 15 respiratory viruses by TaqMan real-time polymerase chain reaction. A sample was considered to be a true positive if any of the specimens was positive. The sensitivities among samples were compared by chi-square test or Fisher's exact test, as appropriate. RESULTS One hundred three triple samples collected consecutively by OPS, NPS, and NW were obtained. In 73 patients, one or more viruses were detected by any of the three methods. Among all viruses, the sensitivity of NPS was significantly higher than that of NW (74% vs. 49%, respectively; p < 0.01) and OPS (74% vs. 49%, respectively; p < 0.01). CONCLUSIONS Flocked NPS collection may be the most effective alternative to NW and OPS for detection of respiratory viruses in adults with acute pharyngitis using TaqMan real-time polymerase chain reaction.
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Affiliation(s)
- Li Li
- Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases (Guangzhou Medical University), The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou 510120, China
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Li L, Chen QY, Li YY, Wang YF, Yang ZF, Zhong NS. Comparison among nasopharyngeal swab, nasal wash, and oropharyngeal swab for respiratory virus detection in adults with acute pharyngitis. BMC Infect Dis 2013; 13:281. [PMID: 23786598 PMCID: PMC3698019 DOI: 10.1186/1471-2334-13-281] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2013] [Accepted: 06/17/2013] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Acute pharyngitis is frequently seen in primary care. Acute viral pharyngitis may be easily misdiagnosed as acute bacterial pharyngitis. Laboratory-confirmed diagnosis of respiratory viruses is recommended. The purpose of this study was to compare the sensitivities among oropharyngeal swab (OPS), nasopharyngeal swab (NPS), and nasal wash (NW) in adults with acute pharyngitis. METHODS OPS, NPS, and NW were obtained from each participant with acute pharyngitis. The specimens were tested for 15 respiratory viruses by TaqMan real-time polymerase chain reaction. A sample was considered to be a true positive if any of the specimens was positive. The sensitivities among samples were compared by chi-square test or Fisher's exact test, as appropriate. RESULTS One hundred three triple samples collected consecutively by OPS, NPS, and NW were obtained. In 73 patients, one or more viruses were detected by any of the three methods. Among all viruses, the sensitivity of NPS was significantly higher than that of NW (74% vs. 49%, respectively; p < 0.01) and OPS (74% vs. 49%, respectively; p < 0.01). CONCLUSIONS Flocked NPS collection may be the most effective alternative to NW and OPS for detection of respiratory viruses in adults with acute pharyngitis using TaqMan real-time polymerase chain reaction.
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Affiliation(s)
- Li Li
- Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Diseases (Guangzhou Medical University), The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou 510120, China
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Rockett RJ, Sloots TP, Bowes S, O'Neill N, Ye S, Robson J, Whiley DM, Lambert SB, Wang D, Nissen MD, Bialasiewicz S. Detection of novel polyomaviruses, TSPyV, HPyV6, HPyV7, HPyV9 and MWPyV in feces, urine, blood, respiratory swabs and cerebrospinal fluid. PLoS One 2013; 8:e62764. [PMID: 23667518 PMCID: PMC3648528 DOI: 10.1371/journal.pone.0062764] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Accepted: 03/24/2013] [Indexed: 11/28/2022] Open
Abstract
Eight novel human polyomaviruses have been discovered since 2007. Prevalence rates and tissue tropism for the most recent members HPyV 6, 7, 9, TSPyV and MWPyV are largely unknown. We used real-time PCR to determine the presence of HPyV 6, 7, 9, TSPyV and MWPyV in feces (n = 263), urine (n = 189), blood (n = 161), respiratory swabs (n = 1385) and cerebrospinal fluid (n = 171) from both healthy control children and children and adults undergoing diagnostic testing. Whole genome sequencing was able to be performed on 9 MWPyV positive specimens. Novel polyomaviruses were only detected in respiratory swabs and feces, with no detections of HPyV 9 in any sample type. MWPyV was found to be the most prevalent novel polyomavirus, being detected in 18 (1.5%) respiratory specimens from symptomatic patients, 16 (9.8%) respiratory sample from healthy control children, 11 (5.9%) fecal specimens from patient suffering gastrointestinal illness, and in 13 (15.3%) of feces from healthy control children. MWPyV was found only in respiratory and fecal specimens from children, the oldest being 9 years old. HPyV 6, 7, 9 and TSPyV were also detected in respiratory specimens and fecal specimens at low prevalence (<1.3%). The majority of these detections were found in immunocompromised patients. Our findings suggest that MWPyV can result in a subclinical infection, persistent or intermittent shedding, particularly in young children. The other novel polyomaviruses were also found in respiratory and fecal specimens, but at lower prevalence and most commonly in immunocompromised individuals.
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Affiliation(s)
- Rebecca J Rockett
- Queensland Paediatric Infectious Diseases Laboratory, Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, Queensland, Australia.
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Tippett E, Clark R. Benign acute childhood myositis following human parainfluenza virus type-1 infection. Emerg Med Australas 2013; 25:248-51. [DOI: 10.1111/1742-6723.12064] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2013] [Indexed: 12/01/2022]
Affiliation(s)
- Emma Tippett
- Department of Emergency Medicine; Royal Brisbane and Women's Hospital; Brisbane; Queensland; Australia
| | - Ronald Clark
- Department of Emergency Medicine; Royal Children's Hospital; Brisbane; Queensland; Australia
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Chang AB, Grimwood K, Wilson AC, van Asperen PP, Byrnes CA, O’Grady KAF, Sloots TP, Robertson CF, Torzillo PJ, McCallum GB, Masters IB, Buntain HM, Mackay IM, Ungerer J, Tuppin J, Morris PS. Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial. Trials 2013; 14:53. [PMID: 23421781 PMCID: PMC3586343 DOI: 10.1186/1745-6215-14-53] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2012] [Accepted: 01/22/2013] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. METHODS This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. DISCUSSION Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. TRIAL REGISTRATION Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879.
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Affiliation(s)
- Anne B Chang
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
- Queensland Children’s Respiratory Centre, Royal Children’s Hospital, Brisbane, QLD, Australia
- Queensland Children’s Medical Research Institute, Brisbane, QLD, Australia
| | - Keith Grimwood
- Queensland Children’s Medical Research Institute, Brisbane, QLD, Australia
- Queensland Paediatric Infectious Diseases Laboratory, Royal Children’s Hospital, Brisbane, QLD, Australia
| | - Andrew C Wilson
- Department of Respiratory Medicine, Princess Margaret Hospital, Perth, Australia
| | - Peter P van Asperen
- Department of Respiratory Medicine, The Children’s Hospital at Westmead and Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Catherine A Byrnes
- Department of Paediatrics, University of Auckland and Starship Children’s Hospital, Auckland, New Zealand
| | | | - Theo P Sloots
- Queensland Children’s Medical Research Institute, Brisbane, QLD, Australia
- Queensland Paediatric Infectious Diseases Laboratory, Royal Children’s Hospital, Brisbane, QLD, Australia
| | - Colin F Robertson
- Department of Respiratory Medicine, Royal Children’s Hospital, Murdoch Children’s Research Institute, University of Melbourne, Melbourne, VIC, Australia
| | | | - Gabrielle B McCallum
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
| | - Ian B Masters
- Queensland Children’s Respiratory Centre, Royal Children’s Hospital, Brisbane, QLD, Australia
- Queensland Children’s Medical Research Institute, Brisbane, QLD, Australia
| | - Helen M Buntain
- Queensland Children’s Respiratory Centre, Royal Children’s Hospital, Brisbane, QLD, Australia
- Queensland Children’s Medical Research Institute, Brisbane, QLD, Australia
| | - Ian M Mackay
- Queensland Children’s Medical Research Institute, Brisbane, QLD, Australia
- Queensland Paediatric Infectious Diseases Laboratory, Royal Children’s Hospital, Brisbane, QLD, Australia
| | - Jacobus Ungerer
- Department Chemical Pathology, Queensland Pathology, Royal Brisbane Hospital, Brisbane, Australia
| | - Joanne Tuppin
- Queensland Children’s Respiratory Centre, Royal Children’s Hospital, Brisbane, QLD, Australia
- Queensland Children’s Medical Research Institute, Brisbane, QLD, Australia
| | - Peter S Morris
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
- Department of Paediatrics, Royal Darwin Hospital, Darwin, NT, Australia
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Abstract
BACKGROUND Viral respiratory infections are among the most common reasons for hospitalization of children in the United States. Our objective was to compare molecular and conventional methods in a cohort of hospitalized children with and without symptoms of respiratory viral illness (RVI). METHODS We conducted a retrospective cohort study of infants and toddlers hospitalized between December 2007 and March 2008 at Johns Hopkins Hospital. Five hundred sixty-nine of 641 patient visits (89%) were tested on admission. Conventional tests (immunochromatography, direct fluorescent antibody, shell vial and tube culture) were performed on all patients and nucleic acid tests (NATs) were performed on available samples (n = 306). Viruses were grouped into those routinely (group 1) and those not routinely (group 2) detected by conventional methods. RESULTS In children with RVI symptoms (n = 148), NATs identified a virus in 83% of specimens compared with 49% by conventional methods (P < 0.001), but detected a similar percentage of specimens with group 1 viruses (48.6% and 55.4%; P = 0.13) compared with conventional tests. In children without RVI symptoms (n = 158), NATs identified a virus in 41.7% of specimens compared with 4.4% by conventional tests (P < 0.001) and identified more group 1 viruses (9.5% and 4.4%; P = 0.03) compared with conventional tests. Group 2 viruses were identified by NATs in a similar percentage of symptomatic and asymptomatic patients (25% and 32.3%; P = 0.20). CONCLUSIONS Molecular assays may have several advantages over conventional methods for detecting respiratory viruses, including improved sensitivity and rapid detection, but given the high prevalence of positive results in children without RVI symptoms, results should be interpreted cautiously.
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Chang AB, Grimwood K, Robertson CF, Wilson AC, van Asperen PP, O’Grady KAF, Sloots TP, Torzillo PJ, Bailey EJ, McCallum GB, Masters IB, Byrnes CA, Chatfield MD, Buntain HM, Mackay IM, Morris PS. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial. Trials 2012; 13:156. [PMID: 22937736 PMCID: PMC3488323 DOI: 10.1186/1745-6215-13-156] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2012] [Accepted: 08/16/2012] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. METHODS We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. DISCUSSION Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel. TRIAL REGISTRATION Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000011886.
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Affiliation(s)
- Anne B Chang
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
- Queensland Children’s Respiratory Centre, Royal Children’s Hospital, Brisbane, QLD, Australia
- Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, QLD, Australia
| | - Keith Grimwood
- Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, QLD, Australia
- Queensland Paediatric Infectious Diseases Laboratory, Royal Children’s Hospital, Brisbane, QLD, Australia
| | - Colin F Robertson
- Department of Respiratory Medicine, Royal Children’s Hospital, Murdoch Children’s Research Institute, University of Melbourne, Melbourne, VIC, Australia
| | - Andrew C Wilson
- Department of Respiratory Medicine, Princess Margaret Hospital, Perth, Australia
| | - Peter P van Asperen
- Department of Respiratory Medicine, The Children’s Hospital at Westmead & Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Kerry-Ann F O’Grady
- Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, QLD, Australia
| | - Theo P Sloots
- Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, QLD, Australia
- Queensland Paediatric Infectious Diseases Laboratory, Royal Children’s Hospital, Brisbane, QLD, Australia
| | | | - Emily J Bailey
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
- Queensland Children’s Respiratory Centre, Royal Children’s Hospital, Brisbane, QLD, Australia
- Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, QLD, Australia
| | - Gabrielle B McCallum
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
| | - Ian B Masters
- Queensland Children’s Respiratory Centre, Royal Children’s Hospital, Brisbane, QLD, Australia
- Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, QLD, Australia
| | - Catherine A Byrnes
- Department of Paediatrics, University of Auckland and Starship Children’s Hospital, Auckland, New Zealand
| | - Mark D Chatfield
- Research and Education Support Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
| | - Helen M Buntain
- Queensland Children’s Respiratory Centre, Royal Children’s Hospital, Brisbane, QLD, Australia
- Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, QLD, Australia
| | - Ian M Mackay
- Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, QLD, Australia
- Queensland Paediatric Infectious Diseases Laboratory, Royal Children’s Hospital, Brisbane, QLD, Australia
| | - Peter S Morris
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
- Department of Paediatrics, Royal Darwin Hospital, Darwin, NT, Australia
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Stelzer-Braid S, Johal H, Skilbeck K, Steller A, Alsubie H, Tovey E, Van Asperen P, McKay K, Rawlinson WD. Detection of viral and bacterial respiratory pathogens in patients with cystic fibrosis. J Virol Methods 2012; 186:109-12. [PMID: 22940004 DOI: 10.1016/j.jviromet.2012.08.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2012] [Revised: 08/08/2012] [Accepted: 08/20/2012] [Indexed: 11/19/2022]
Abstract
The presence of viral respiratory infections is associated closely with exacerbations in patients with cystic fibrosis. Viral and bacterial multiplex PCRs were developed and applied to nasal swab samples from children with cystic fibrosis. This showed a large number of individuals with cystic fibrosis were infected with rhinoviruses, and more were infected with viral than bacterial pathogens. All individuals with parainfluenza 3 virus had clinical exacerbations of their cystic fibrosis, and although 3/4 of these children were co-infected with HRV. The findings do not suggest a significant association for any other virus or bacteria with exacerbation. There is clear evidence some viral infections are associated with cystic fibrosis that dual infection is more likely to produce symptoms, and mechanisms of viral-induced exacerbation should be elucidated.
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Affiliation(s)
- Sacha Stelzer-Braid
- Virology Division, SEALS Microbiology, Prince of Wales Hospital, Randwick, NSW 2031, Australia
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Puppe W, Weigl J, Gröndahl B, Knuf M, Rockahr S, von Bismarck P, Aron G, Niesters HGM, Osterhaus ADME, Schmitt HJ. Validation of a multiplex reverse transcriptase PCR ELISA for the detection of 19 respiratory tract pathogens. Infection 2012; 41:77-91. [PMID: 22847627 PMCID: PMC7100787 DOI: 10.1007/s15010-012-0298-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Accepted: 06/30/2012] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Since acute respiratory tract infections inflict a high burden of disease in children worldwide, a multiplex reverse transcription polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) to detect 19 different respiratory pathogens was developed and validated. METHODS A total of 430 respiratory specimens were retrospectively tested in parallel by both the advanced 19-valent m-RT-PCR-ELISA as well as by culture or individual RT-PCR assays used in clinical routine. RESULTS The mean (median) sensitivity of the m-RT-PCR-ELISA in the retrospective test was 93.3% (95.1%; range 83.3-100 %), and the mean (median) specificity was 99.8 and 100 % (range 98.6-100 %), respectively. The mean positive predictive value was 99.3 % (range 93.4-100 %) and the mean negative predictive value was 95.3 % (range 98.4-100 %). Feasibility and clinical value of the 19-valent method was prospectively shown on 16,231 incoming clinical specimens from patients between 0 and 16 years of age with acute respiratory tract infections admitted to pediatric hospitals or private practices from October 2003 to June 2010 in three regions in Germany (Kiel, Mainz, Freiburg; Freiburg to June 2007 only). At least one microorganism was detected in 10,765 of 16,231 (66.3 %) clinical specimens: 5,044 RV, 1,999 RSV, 1,286 AV, 944 EV, 737 seasonal IVA, 173 pandemic IVA H1N1-2009, 899 MPV, 518 CV, 383 PIV3, 268 PIV1, 259 Mpn, 205 IVB, 164 PIV2, 144 PIV4, 103 Bp, 29 Cpn and 29 Bpp, while reovirus and Lpn were not present in these specimens from a pediatric population. More than one organism could be detected in 13.4 % of the specimens. CONCLUSIONS The m-RT-PCR-ELISA evaluated here improves the spectrum for diagnosing respiratory infections and is a feasible instrument for individual diagnostic and epidemiological studies.
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Affiliation(s)
- W Puppe
- Pediatric Infectious Diseases, Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105, Kiel, Germany
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Co-circulation of four human coronaviruses (HCoVs) in Queensland children with acute respiratory tract illnesses in 2004. Viruses 2012; 4:637-53. [PMID: 22590689 PMCID: PMC3347326 DOI: 10.3390/v4040637] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Revised: 04/11/2012] [Accepted: 04/11/2012] [Indexed: 11/16/2022] Open
Abstract
Acute respiratory illnesses (ARIs) with unconfirmed infectious aetiologies peak at different times of the year. Molecular diagnostic assays reduce the number of unconfirmed ARIs compared to serology- or culture-based techniques. Screening of 888 inpatient and outpatient respiratory specimens spanning late autumn through to early spring, 2004, identified the presence of a human coronavirus (HCoV) on 74 occasions (8.3% of all specimens and 26.3% of all respiratory virus detections). Prevalence peaked in August (late winter in the southern hemisphere) when they were detected in 21.9% of specimens tested. HCoV-HKU1 and HCoV-OC43 comprised 82.4% of all HCoVs detected. Positive specimens were used to develop novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. An objective clinical severity score was assigned to each positive HCoV patient. Severity scores were similar to those from a random selection of young children who were positive for respiratory syncytial virus at a different time but from the same specimen population. During the cooler months of 2004, sensitive and specific RT-rtPCRs identified the concurrent circulation of all four HCoVs, a quarter of which co-occurred with another virus and most of which were from children under the age of two years.
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Mahony JB, Petrich A, Smieja M. Molecular diagnosis of respiratory virus infections. Crit Rev Clin Lab Sci 2012; 48:217-49. [PMID: 22185616 DOI: 10.3109/10408363.2011.640976] [Citation(s) in RCA: 134] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The appearance of eight new respiratory viruses, including the SARS coronavirus in 2003 and swine-origin influenza A/H1N1 in 2009, in the human population in the past nine years has tested the ability of virology laboratories to develop diagnostic tests to identify these viruses. Nucleic acid based amplification tests (NATs) for respiratory viruses were first introduced two decades ago and today are utilized for the detection of both conventional and emerging viruses. These tests are more sensitive than other diagnostic approaches, including virus isolation in cell culture, shell vial culture (SVC), antigen detection by direct fluorescent antibody (DFA) staining, and rapid enzyme immunoassay (EIA), and now form the backbone of clinical virology laboratory testing around the world. NATs not only provide fast, accurate and sensitive detection of respiratory viruses in clinical specimens but also have increased our understanding of the epidemiology of both new emerging viruses such as the pandemic H1N1 influenza virus of 2009, and conventional viruses such as the common cold viruses, including rhinovirus and coronavirus. Multiplex polymerase chain reaction (PCR) assays introduced in the last five years detect up to 19 different viruses in a single test. Several multiplex PCR tests are now commercially available and tests are working their way into clinical laboratories. The final chapter in the evolution of respiratory virus diagnostics has been the addition of allelic discrimination and detection of single nucleotide polymorphisms associated with antiviral resistance. These assays are now being multiplexed with primary detection and subtyping assays, especially in the case of influenza virus. These resistance assays, together with viral load assays, will enable clinical laboratories to provide physicians with new and important information for optimal treatment of respiratory virus infections.
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Affiliation(s)
- James B Mahony
- M.G. DeGroote Institute for Infectious Disease Research, St. Joseph’s Healthcare, Hamilton, Canada.
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Popow-Kraupp T, Aberle JH. Diagnosis of respiratory syncytial virus infection. Open Microbiol J 2011; 5:128-34. [PMID: 22262985 PMCID: PMC3258569 DOI: 10.2174/1874285801105010128] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2011] [Revised: 10/12/2011] [Accepted: 10/27/2011] [Indexed: 02/07/2023] Open
Abstract
Respiratory syncytial virus (RSV) is one of the most important pathogen causing severe lower respiratory tract infections in all age groups often requiring hospitalization. Rapid laboratory diagnosis of RSV infection significantly decreases the use of antibiotics, additional laboratory testing and is associated with shorter hospitalization periods. The specific diagnosis of RSV infection is based on the detection of virus or viral antigens or virus specific nucleic acid sequences in respiratory secretions. The kind and quality of the clinical specimen exerts a considerable influence on the results of all currently used viral detection assays. Antigen based tests are widely available, easy to perform and the results are available in a short time but their reduced sensitivity and specificity represent a considerable shortcoming. Among the methods available isolation in cell culture was considered the gold standard for the sensitive identification of RSV but is gradually replaced by highly sensitive and specific nucleic acid amplification assays that provide more rapid results. Of these reverse transcription polymerase chain reaction (PCR) was the first and is still the most frequently used nucleic acid-based assay. New methodologies, as for example the real-time PCR methods allow the quantification of viral nucleic acids in the clinical sample. Disadvantages of the nucleic acid based assays are their high costs and their limited standardization. Future research on new methodologies for the diagnosis of viral respiratory tract infections should focus on the development of sensitive, rapid and cost effective test systems allowing the screening for all probable causative agents. In addition varying testing protocols for summer and winter months based on epidemiologic data are needed to direct their practical use.
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Sovero M, Garcia J, Kochel T, Laguna-Torres VA, Gomez J, Chicaiza W, Barrantes M, Sanchez F, Jimenez M, Comach G, de Rivera IL, Arango AE, Agudo R, Halsey ES. Circulating strains of human respiratory syncytial virus in central and south America. PLoS One 2011; 6:e22111. [PMID: 21829605 PMCID: PMC3148217 DOI: 10.1371/journal.pone.0022111] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2011] [Accepted: 06/15/2011] [Indexed: 11/18/2022] Open
Abstract
Human respiratory syncytial virus (HRSV) is a major cause of viral lower respiratory tract infections among infants and young children. HRSV strains vary genetically and antigenically and have been classified into two broad subgroups, A and B (HRSV-A and HRSV-B, respectively). To date, little is known about the circulating strains of HRSV in Latin America. We have evaluated the genetic diversity of 96 HRSV strains by sequencing a variable region of the G protein gene of isolates collected from 2007 to 2009 in Central and South America. Our results show the presence of the two antigenic subgroups of HRSV during this period with the majority belonging to the genotype HRSV-A2.
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Affiliation(s)
- Merly Sovero
- United States Naval Medical Research Unit 6, Lima, Peru
| | - Josefina Garcia
- United States Naval Medical Research Unit 6, Lima, Peru
- * E-mail:
| | | | | | - Jorge Gomez
- Dirección General de Epidemiología, Ministerio de Salud, Lima, Perú
| | | | | | - Felix Sanchez
- Hospital Infantil Manuel de Jesus Rivera, Managua, Nicaragua
| | | | | | | | | | - Roberto Agudo
- Dirección General de Epidemiología, Ministerio de Salud, Cochabamba, Bolivia
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Gharabaghi F, Hawan A, Drews SJ, Richardson SE. Evaluation of multiple commercial molecular and conventional diagnostic assays for the detection of respiratory viruses in children. Clin Microbiol Infect 2011; 17:1900-6. [PMID: 21707834 PMCID: PMC7128441 DOI: 10.1111/j.1469-0691.2011.03529.x] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Clin Microbiol Infect 2011; 17: 1900–1906 Abstract This study compares the performance of four commercial multiplex PCR assays (Resplex II Panel v2.0, Seeplex RV15, xTAG RVP and xTAG RVP Fast) and direct fluorescent antibody (DFA) staining and viral isolation. Seven hundred and fifty nasopharyngeal swabs were tested for 17 viral agents. In each assay, the sensitivity and specificity for each target were determined against a composite reference standard. Two hundred and eighty‐eight out of 750 (38.4%) specimens were positive by DFA or viral isolation, while an additional 214 (28.5%) were positive by multiplex PCR, for a total positivity rate of 66.9%. Of 502 positive specimens, one virus was detected in 420 specimens (83.7%), two in 77 (15.3%), three in four (0.8%) and four in one case (0.2%). Compared with a composite reference standard, the inter‐assay accuracy of the multiplex PCR assays varied, but all were superior to conventional diagnostic methods in detecting a broad range of respiratory viral agents in children. In addition, the sensitivity of two commercial assays, Resplex II Plus PRE and Seeplex Influenza A/B Subtyping, was determined relative to the Astra influenza Screen & Type assay for detection of influenza A viruses, including seasonal influenzas and pandemic H1N1 2009 influenza A virus. Using 75 positive and 55 negative nasopharyngeal swabs for influenza A by the Astra assay, the sensitivity of Seeplex and Resplex was 95.9% and 91.8%, respectively, with a specificity of 100% for both.
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Affiliation(s)
- F Gharabaghi
- Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada.
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Binks MJ, Cheng AC, Smith-Vaughan H, Sloots T, Nissen M, Whiley D, McDonnell J, Leach AJ. Viral-bacterial co-infection in Australian Indigenous children with acute otitis media. BMC Infect Dis 2011; 11:161. [PMID: 21649905 PMCID: PMC3128050 DOI: 10.1186/1471-2334-11-161] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2011] [Accepted: 06/07/2011] [Indexed: 11/24/2022] Open
Abstract
Background Acute otitis media with perforation (AOMwiP) affects 40% of remote Indigenous children during the first 18 months of life. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the primary bacterial pathogens of otitis media and their loads predict clinical ear state. Our hypothesis is that antecedent respiratory viral infection increases bacterial density and progression to perforation. Methods A total of 366 nasopharyngeal swabs from 114 Indigenous children were retrospectively examined. A panel of 17 respiratory viruses was screened by PCR, and densities of S. pneumoniae, H. influenzae and M. catarrhalis were estimated by quantitative real time PCR. Data are reported by clinical ear state. Results M. catarrhalis (96%), H. influenzae (91%), S. pneumoniae (89%) and respiratory viruses (59%) were common; including rhinovirus (HRV) (38%), polyomavirus (HPyV) (14%), adenovirus (HAdV) (13%), bocavirus (HBoV) (8%) and coronavirus (HCoV) (4%). Geometric mean bacterial loads were significantly higher in children with acute otitis media (AOM) compared to children without evidence of otitis media. Children infected with HAdV were 3 times more likely (p < 0.001) to have AOM with or without perforation. Conclusion This study confirms a positive association between nasopharyngeal bacterial load and clinical ear state, exacerbated by respiratory viruses, in Indigenous children. HAdV was independently associated with acute ear states.
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Affiliation(s)
- Michael J Binks
- Ear and Respiratory Unit, Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
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Sánchez-Yebra W, Ávila-Carrillo JA, Giménez-Sánchez F, Reyes-Bertos A, Sánchez-Forte M, Morales-Torres M, Rojas A, Mendoza J. Viral agents causing lower respiratory tract infections in hospitalized children: evaluation of the Speed-Oligo® RSV assay for the detection of respiratory syncytial virus. Eur J Clin Microbiol Infect Dis 2011; 31:243-50. [PMID: 21647616 PMCID: PMC7088155 DOI: 10.1007/s10096-011-1300-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2011] [Accepted: 05/15/2011] [Indexed: 11/01/2022]
Abstract
Respiratory syncytial virus (RSV) is the viral agent which is more frequently involved in lower respiratory tract infections (LRTIs) in infants under 1 year of age in developed countries. A new oligochromatographic assay, Speed-Oligo® RSV, was designed and optimized for the specific detection and identification of RSV subtypes A and B. The test was evaluated in 289 clinical samples from 169 hospitalized children using an immunochromatography (IC) test, virus isolation by culture, and an in-house real-time polymerase chain reaction (RT-PCR). Other viruses causing LRTIs were investigated by cell culture or PCR-based tests. Sixty-two patients were infected by RSV (36.7%). In addition, adenovirus, influenza B, parainfluenza 2, and human metapneumovirus were detected in rates ranging from 5 to 8%. A proportion of 10.1% of the patients had mixed infections. The sensitivity, specificity, and positive and negative predictive values were, respectively, 94.9, 99.4, 98.9, and 97.4% for Speed-Oligo® RSV, 92.9, 96.3, 92.9, and 96.3% for RT-PCR/RSV, and 58.4, 98.1, 93.3, and 82.6% for IC. Our rates of viral detection and co-infection were similar to those of previously reported series. Finally, we find that Speed-Oligo® RSV is a rapid and easy-to-perform technique for the detection of RSV and the identification of subtypes A and B.
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Affiliation(s)
- W Sánchez-Yebra
- Department of Microbiology, CH Torrecárdenas, 04009, Almería, Spain.
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