VIRULENCE 2016, VOL. 7, NO. 7, 740–741 http://dx.doi.org/10.1080/21505594.2016.1204062
EDITORIAL
Setting a trap for respiratory viruses Erik A. Karlsson Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA ARTICLE HISTORY Received 15 June 2016; Accepted 15 June 2016 KEYWORDS clinical diagnostics; coronavirus; influenza; molecular detection; respiratory syncytial virus; respiratory virus; surveillance
Seasonal respiratory virus infections represent a significant burden on global public health, especially in highrisk groups such as children and immunocompromised populations. In any given year, influenza virus alone infects 5–15% of the world population resulting in 3–5 million cases of severe illness and 500,000 deaths1 and respiratory syncytial virus (RSV), the leading cause of acute respiratory infections in children, claims between 66,000 and 234,000 infants and young children.2 Additional yearly morbidity and mortality is associated with a number of other viruses including parainfluenza virus, human metapneumoviurs, rhinovirus, adenovirus and coronavirus (CoV). Apart from seasonal outbreaks, these viruses tend to be evolutionarily dynamic in nature resulting in frequent emergence and reemergence of novel strains. Within the past 2 decades, the world has seen a pandemic of novel A(H1N1) influenza, numerous human infections with avian influenza subtypes such as A(H5N1), A(H7N9) and A(H6N1) and the emergence and spread of 2 novel coronaviruses, Severe Acute Respiratory Syndrome (SARS)-CoV and Middle East Respiratory Syndrome (MERS)-CoV.3 Therefore, accurate and efficient identification of respiratory viruses is critical for the management of infection, both in the context of seasonal outbreaks or during a pandemic event. While viruses are the most common infectious agent of the respiratory tract, respiratory virus infection cannot be reliably diagnosed on clinical characteristics alone since symptoms are not specific for viral or bacterial etiology. Laboratory identification and isolation has been a vital component of respiratory infection treatment, prevention and control since the discovery of influenza virus in 1933.4,5 Traditional methods of diagnosis rely on isolation and propagation of virus in the appropriate culture system; however, these techniques have limited clinical usefulness due to a number of factors including assay time, expertise required for accurate interpretation
and lack of adequate systems for all viruses. The advent of molecular detection of viral nucleic acids from respiratory viruses has revolutionized laboratory diagnosis and surveillance of viral pathogens, and these types of tests have begun to supplant traditional laboratory methodology. Nevertheless, while these nucleic acid amplification tests have increased sensitivity and decreased diagnostic time immensely problems still exist with false negative or low values further work on improving these tests is warranted.6-8 The work by Shafagati et al.9 presented in this issue represents an advancement for the clinical diagnosis of respiratory pathogens. While previous studies from this group have demonstrated that Nanotrap particles can effectively and rapidly capture a number of pathogens,10 in this article, Shafagati et al.9 utilize this technology to concentrate virus from clinically relevant, human specimens. Incubation with Nanotrap particles prior to nucleic acid extraction enhanced detection of several subtypes of seasonal influenza virus and avian influenza virus as well as CoV and RSV from nasal aspirates, nasal swabs and saliva. For influenza alone, detection capacity was increased 7 to 10-fold. Additionally, since respiratory virus coinfection do occur in up to 30% of acute respiratory tract infections in children,11 the authors show that these particles can enhance the detection of multiple respiratory viruses from a single sample. These results present a boon not only for increased sensitivity of laboratory diagnosis but also for other clinical and epidemiological aspects of respiratory virus pathogenesis and transmission. Enhanced detection could prolong the ability to identify virus following infection or onset of symptoms giving a better clinical and epidemiological picture of viral shed. Furthermore, these techniques could be applied to asymptomatic or contact individuals at high risk of viral exposure due to proximity to infected individuals or potential sources of zoonotic transmission.
CONTACT Erik A. Karlsson [email protected] St. Jude Children’s Research Hospital, MS #320, 262 Danny Thomas Place, Memphis, TN 38105, USA. Comment on: Shafagati N, et al. Enhanced detection of respiratory pathogens with nanotrap particles. Virulence 2016; 7(7):756-769; http://dx.doi.org/10.1080/ 21505594.2016.1185585 © 2016 Taylor & Francis
VIRULENCE
New techniques to concentrate and enhance detection of respiratory viruses such as the one presented by Shafagati et al.9 provide an advantage not only for rapid diagnosis of human infections but also to increase the sensitivity of early detection surveillance systems. Infectious disease surveillance systems are critical for enacting prompt control or preventative measures to prevent widespread outbreak. Started in 1948, the World Health Organization global influenza surveillance network involves 110 collaborating laboratories in 82 countries that constantly monitor and isolate influenza viruses from humans and animals. This data is crucial for a coordinated and unified response for the seasonal and pandemic control of influenza.12 One limitation of influenza surveillance is the ability to detect virus in environmental and animal samples that may have very low viral abundance. Therefore, concentration with Nanotrap particles may increase detection of influenza in these samples. Moreover, in their article, the authors show that Nanotrap particles not only increase molecular detection but can also be used to increase viral isolation. Enhanced isolation of influenza viruses from both animals and humans would be invaluable not only for understanding influenza epidemiology and pathogenesis but also provide increased resources for rapid vaccine development. Similar advantages could also be applied to similar surveillance systems, such as the search for CoV in humans, camels and bats. Overall, the results from the study by Shafagati et al.9 presented in this issue of Virulence represent an interesting step forward in molecular detection and isolation of respiratory viruses; however, several limitations still exist. Further work is warranted on understanding the exact mechanism or mechanisms by which these Nanotrap particles bind to virus and how different particles could be harnessed to multiplex from individual samples. In addition, additional study should be done to utilize these particles with many more viruses and individual viable viral subtypes as well as relevant matrices (ie: avian and human stool and other mammalian nasal aspirates) to determine the full capability of individual particle types. Finally, all of these results should be validated by multiple teams to determine the extent of usefulness of the Nanotrap particles in both the clinical laboratory and field settings.
741
Disclosure of potential conflicts of interest No potential conflicts of interest were disclosed.
References [1] Advisory Committee on Immunization Practices Prevention and Control of Influenza. Recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2006; 55:1-42. [2] Acosta PL, Caballero MT, Polack FP. Brief history and characterization of enhanced respiratory syncytial virus disease. Clin Vaccine Immunol 2016; 23:189-95; PMID:26677198; http://dx.doi.org/10.1128/CVI.00609-15 [3] Hui DS, Zumla A. Emerging respiratory tract viral infections. Curr Opin Pulmonary Med 2015; 21:284-92; PMID:25764021; http://dx.doi.org/10.1097/MCP.000000000 0000153 [4] Smith W, Andrewes CH, Laidlaw PP. A virus obtained from influenza patients. The Lancet 1933; 222:66-8; http://dx.doi.org/10.1016/S0140-6736(00)78541-2 [5] Wozniak-Kosek A, Kempinska-Miroslawska B, Hoser G. Detection of the influenza virus yesterday and now. Acta biochimica Polonica 2014; 61:465-70; PMID:25180218 [6] Shojaei TR, Tabatabaei M, Shawky S, Salleh MA, Bald D. A review on emerging diagnostic assay for viral detection: the case of avian influenza virus. Mol Biol Rep 2015; 42:187-99; PMID:25245956; http://dx.doi.org/10.1007/ s11033-014-3758-5 [7] Buller RS. Molecular detection of respiratory viruses. Clin Lab Med 2013; 33:439-60; PMID:23931834; http://dx.doi. org/10.1016/j.cll.2013.03.007 [8] Peaper DR, Landry ML. Rapid diagnosis of influenza: state of the art. Clin Lab Med 2014; 34:365-85; PMID:24856533; http://dx.doi.org/10.1016/j.cll.2014.02.009 [9] Shafagati N, Fite K, Patanarut A, Baer A, Pinkham C, An S, Foote B, Lepene B, Kehn-Hall K. Enhanced detection of respiratory pathogens with nanotrap particles. Virulence 2016; 7(7): 756-769; http://dx.doi.org/10.1080/ 21505594.2016.1185585 [10] Shafagati N, Patanarut A, Luchini A, Lundberg L, Bailey C, Petricoin E, 3rd, Liotta L, Narayanan A, Lepene B, Kehn-Hall K. The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics. Pathogens Dis 2014; 71:164-76; PMID:24449537; http://dx.doi. org/10.1111/2049-632X.12136 [11] Asner SA, Science ME, Tran D, Smieja M, Merglen A, Mertz D. Clinical disease severity of respiratory viral co-infection versus single viral infection: a systematic review and metaanalysis. PLoS One 2014; 9:e99392; PMID:24932493; http:// dx.doi.org/10.1371/journal.pone.0099392 [12] World Health Organization. Fact Sheet #200: Global infectious disease surveillance. 2016. Retrieved 12 June 2016 from http://www.who.int/mediacentre/factsheets/fs200/en/
EDITORIAL
Setting a trap for respiratory viruses Erik A. Karlsson Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, USA ARTICLE HISTORY Received 15 June 2016; Accepted 15 June 2016 KEYWORDS clinical diagnostics; coronavirus; influenza; molecular detection; respiratory syncytial virus; respiratory virus; surveillance
Seasonal respiratory virus infections represent a significant burden on global public health, especially in highrisk groups such as children and immunocompromised populations. In any given year, influenza virus alone infects 5–15% of the world population resulting in 3–5 million cases of severe illness and 500,000 deaths1 and respiratory syncytial virus (RSV), the leading cause of acute respiratory infections in children, claims between 66,000 and 234,000 infants and young children.2 Additional yearly morbidity and mortality is associated with a number of other viruses including parainfluenza virus, human metapneumoviurs, rhinovirus, adenovirus and coronavirus (CoV). Apart from seasonal outbreaks, these viruses tend to be evolutionarily dynamic in nature resulting in frequent emergence and reemergence of novel strains. Within the past 2 decades, the world has seen a pandemic of novel A(H1N1) influenza, numerous human infections with avian influenza subtypes such as A(H5N1), A(H7N9) and A(H6N1) and the emergence and spread of 2 novel coronaviruses, Severe Acute Respiratory Syndrome (SARS)-CoV and Middle East Respiratory Syndrome (MERS)-CoV.3 Therefore, accurate and efficient identification of respiratory viruses is critical for the management of infection, both in the context of seasonal outbreaks or during a pandemic event. While viruses are the most common infectious agent of the respiratory tract, respiratory virus infection cannot be reliably diagnosed on clinical characteristics alone since symptoms are not specific for viral or bacterial etiology. Laboratory identification and isolation has been a vital component of respiratory infection treatment, prevention and control since the discovery of influenza virus in 1933.4,5 Traditional methods of diagnosis rely on isolation and propagation of virus in the appropriate culture system; however, these techniques have limited clinical usefulness due to a number of factors including assay time, expertise required for accurate interpretation
and lack of adequate systems for all viruses. The advent of molecular detection of viral nucleic acids from respiratory viruses has revolutionized laboratory diagnosis and surveillance of viral pathogens, and these types of tests have begun to supplant traditional laboratory methodology. Nevertheless, while these nucleic acid amplification tests have increased sensitivity and decreased diagnostic time immensely problems still exist with false negative or low values further work on improving these tests is warranted.6-8 The work by Shafagati et al.9 presented in this issue represents an advancement for the clinical diagnosis of respiratory pathogens. While previous studies from this group have demonstrated that Nanotrap particles can effectively and rapidly capture a number of pathogens,10 in this article, Shafagati et al.9 utilize this technology to concentrate virus from clinically relevant, human specimens. Incubation with Nanotrap particles prior to nucleic acid extraction enhanced detection of several subtypes of seasonal influenza virus and avian influenza virus as well as CoV and RSV from nasal aspirates, nasal swabs and saliva. For influenza alone, detection capacity was increased 7 to 10-fold. Additionally, since respiratory virus coinfection do occur in up to 30% of acute respiratory tract infections in children,11 the authors show that these particles can enhance the detection of multiple respiratory viruses from a single sample. These results present a boon not only for increased sensitivity of laboratory diagnosis but also for other clinical and epidemiological aspects of respiratory virus pathogenesis and transmission. Enhanced detection could prolong the ability to identify virus following infection or onset of symptoms giving a better clinical and epidemiological picture of viral shed. Furthermore, these techniques could be applied to asymptomatic or contact individuals at high risk of viral exposure due to proximity to infected individuals or potential sources of zoonotic transmission.
CONTACT Erik A. Karlsson [email protected] St. Jude Children’s Research Hospital, MS #320, 262 Danny Thomas Place, Memphis, TN 38105, USA. Comment on: Shafagati N, et al. Enhanced detection of respiratory pathogens with nanotrap particles. Virulence 2016; 7(7):756-769; http://dx.doi.org/10.1080/ 21505594.2016.1185585 © 2016 Taylor & Francis
VIRULENCE
New techniques to concentrate and enhance detection of respiratory viruses such as the one presented by Shafagati et al.9 provide an advantage not only for rapid diagnosis of human infections but also to increase the sensitivity of early detection surveillance systems. Infectious disease surveillance systems are critical for enacting prompt control or preventative measures to prevent widespread outbreak. Started in 1948, the World Health Organization global influenza surveillance network involves 110 collaborating laboratories in 82 countries that constantly monitor and isolate influenza viruses from humans and animals. This data is crucial for a coordinated and unified response for the seasonal and pandemic control of influenza.12 One limitation of influenza surveillance is the ability to detect virus in environmental and animal samples that may have very low viral abundance. Therefore, concentration with Nanotrap particles may increase detection of influenza in these samples. Moreover, in their article, the authors show that Nanotrap particles not only increase molecular detection but can also be used to increase viral isolation. Enhanced isolation of influenza viruses from both animals and humans would be invaluable not only for understanding influenza epidemiology and pathogenesis but also provide increased resources for rapid vaccine development. Similar advantages could also be applied to similar surveillance systems, such as the search for CoV in humans, camels and bats. Overall, the results from the study by Shafagati et al.9 presented in this issue of Virulence represent an interesting step forward in molecular detection and isolation of respiratory viruses; however, several limitations still exist. Further work is warranted on understanding the exact mechanism or mechanisms by which these Nanotrap particles bind to virus and how different particles could be harnessed to multiplex from individual samples. In addition, additional study should be done to utilize these particles with many more viruses and individual viable viral subtypes as well as relevant matrices (ie: avian and human stool and other mammalian nasal aspirates) to determine the full capability of individual particle types. Finally, all of these results should be validated by multiple teams to determine the extent of usefulness of the Nanotrap particles in both the clinical laboratory and field settings.
741
Disclosure of potential conflicts of interest No potential conflicts of interest were disclosed.
References [1] Advisory Committee on Immunization Practices Prevention and Control of Influenza. Recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2006; 55:1-42. [2] Acosta PL, Caballero MT, Polack FP. Brief history and characterization of enhanced respiratory syncytial virus disease. Clin Vaccine Immunol 2016; 23:189-95; PMID:26677198; http://dx.doi.org/10.1128/CVI.00609-15 [3] Hui DS, Zumla A. Emerging respiratory tract viral infections. Curr Opin Pulmonary Med 2015; 21:284-92; PMID:25764021; http://dx.doi.org/10.1097/MCP.000000000 0000153 [4] Smith W, Andrewes CH, Laidlaw PP. A virus obtained from influenza patients. The Lancet 1933; 222:66-8; http://dx.doi.org/10.1016/S0140-6736(00)78541-2 [5] Wozniak-Kosek A, Kempinska-Miroslawska B, Hoser G. Detection of the influenza virus yesterday and now. Acta biochimica Polonica 2014; 61:465-70; PMID:25180218 [6] Shojaei TR, Tabatabaei M, Shawky S, Salleh MA, Bald D. A review on emerging diagnostic assay for viral detection: the case of avian influenza virus. Mol Biol Rep 2015; 42:187-99; PMID:25245956; http://dx.doi.org/10.1007/ s11033-014-3758-5 [7] Buller RS. Molecular detection of respiratory viruses. Clin Lab Med 2013; 33:439-60; PMID:23931834; http://dx.doi. org/10.1016/j.cll.2013.03.007 [8] Peaper DR, Landry ML. Rapid diagnosis of influenza: state of the art. Clin Lab Med 2014; 34:365-85; PMID:24856533; http://dx.doi.org/10.1016/j.cll.2014.02.009 [9] Shafagati N, Fite K, Patanarut A, Baer A, Pinkham C, An S, Foote B, Lepene B, Kehn-Hall K. Enhanced detection of respiratory pathogens with nanotrap particles. Virulence 2016; 7(7): 756-769; http://dx.doi.org/10.1080/ 21505594.2016.1185585 [10] Shafagati N, Patanarut A, Luchini A, Lundberg L, Bailey C, Petricoin E, 3rd, Liotta L, Narayanan A, Lepene B, Kehn-Hall K. The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics. Pathogens Dis 2014; 71:164-76; PMID:24449537; http://dx.doi. org/10.1111/2049-632X.12136 [11] Asner SA, Science ME, Tran D, Smieja M, Merglen A, Mertz D. Clinical disease severity of respiratory viral co-infection versus single viral infection: a systematic review and metaanalysis. PLoS One 2014; 9:e99392; PMID:24932493; http:// dx.doi.org/10.1371/journal.pone.0099392 [12] World Health Organization. Fact Sheet #200: Global infectious disease surveillance. 2016. Retrieved 12 June 2016 from http://www.who.int/mediacentre/factsheets/fs200/en/
