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Understanding enterovirus 71 infection and neuropathogenesis: perspective from human and animal model studies
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PATHOLOGY 2014 ABSTRACT SUPPLEMENT
2. Tanino M, Sasajima T, Nanjo H, et al. Rapid immunohistochemistry based on alternating current electric field for intraoperative diagnosis of brain tumors. Brain Tumor Pathol 2014; May 8: (Epub ahead of print).
Infectious Diseases and Tropical Disease Pathology: SC16-1 NEEDLE IN A HAYSTACK: THE NEW WORLD OF DIAGNOSTICS FOR MICRO-ORGANISMS Danny Arnold Milner Jr Brigham and Womens’ Hospital, Boston, Massachusetts, USA Infectious disease diagnostics from tissue specimens has relied upon either the presence of a tissue reaction specific to an infection type or morphological identification of an organism for the last century or more. Molecular diagnostics (the detection of RNA or DNA) from a micro-organism in a sample offers the promise of ultra-sensitive testing for patient care but requires careful selection and use for each patient. Examples of successful approaches include confirmation of species of mycobacteria in AFB-positive case using consensus primers and sequencing, confirmation of species of fungi in sections showing fungal forms using consensus primers and sequencing, and organism specific confirmatory PCR on suspicious lesions. Similarly, clinical laboratory panels for GI pathogens and respiratory pathogens are growing in popularity for rapid screening and accurate diagnosis across a range of organisms. As with cancer diagnostics, one of the next phases of microorganism detection will be for the expression profile or pattern of specific genes which not only identify the organism but provide information on drug resistance, behavior, prognosis, and treatment. A discussion of how these technologies work in basic science are moving into the forefront of patient care will be presented with examples.
Infectious Diseases and Tropical Disease Pathology: SC16-1 rRNA SEQUENCING IN MOLECULAR MICROBIOLOGICAL DIAGNOSIS OF BACTERIAL INFECTIONS IN THE AUTOPSY SETTING John D. Hart1,2,3, Teresa Street3, John M. Wrightson3, David P. Moore4,5, Anthony G. Scott6, Derrick W. Crook3 and Gareth D. H. Turner7,8,9 1University of Malawi College of Medicine, Mahatma Gandhi Road, Blantyre, Malawi, 2London School of Hygiene and Tropical Medicine, Keppel Street, London, UK, 3Department of Microbiology, Nuffield Department of Medicine, Oxford University, John Radcliffe Hospital, Oxford, UK, 4Faculty of Health Sciences, University of the Witwatersrand, Chris Hani Baragwanath Hospital, Johannesburg, South Africa, 5Department of Paediatrics and Child Health, Metabolic Unit, Chris Hani Baragwanath Hospital, Johannesburg, South Africa, 6KEMRIWellcome Trust Research Programme, Kilifi, Kenya, 7Centre for Tropical Diseases, Nuffield Department of Medicine, Oxford University, John Radcliffe Hospital, Oxford, UK, 8Department of Cellular Pathology, Oxford University, John Radcliffe Hospital, Oxford, UK, and 9Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Pathology (2014), 46(S2)
Diagnosing the aetiology of infectious diseases at autopsy, such as pneumonia, meningitis, sepsis or SUDI, is complicated due to issues including post mortem contamination, difficulty culturing fastidious organisms and subjective interpretation of polymicrobial cultures. Death of organisms may also occur post mortem, especially if antibiotics were given to the patient, but residual DNA from non-viable organisms, amenable to molecular detection, may remain. The 16S rRNA gene is present in all bacteria with conserved and hyper-variable regions along its length, allowing amplification and sequencing of all bacterial 16S sequences present in a sample. 16S sequencing offers potential advantages over culture-based diagnostics and is increasingly used in clinical practice. It has been used to identify bacteria in formalin fixed paraffin embedded (FFPE) surgical pathology specimens but its use has not been reported in autopsy diagnosis. This talk will summarise a study aimed to assess the utility of 16S sequencing as an adjunctive microbiological test in the autopsy. Our preliminary work has used post mortem lung tissue samples from children dying with pneumonia as part of the Pneumonia Etiology Research for Child Health (PERCH) project. The technique has identified known pathogens in some cases and provided additional diagnostic information in others. The presentation will discuss the technical aspects of 16S sequencing from FFPE and autopsy material, and the issues surrounding its application to diagnosis in comparison with standard culture based diagnostics on surgical/autopsy material.
Infectious Diseases and Tropical Disease Pathology: SS16-1 UNDERSTANDING ENTEROVIRUS 71 INFECTION AND NEUROPATHOGENESIS: PERSPECTIVE FROM HUMAN AND ANIMAL MODEL STUDIES Kum Thong Wong1 and Kien Chai ONg2 1Department of Pathology, Faculty of Medicine, University of Malaya, and 2Department of Biomedical Science, Faculty of Medicine, University of Malaya, Malaysia Enterovirus 71 (EV71) (family Picornaviridae, genus Human Enterovirus A) causes the relatively mild hand, foot and mouth disease in children. However, rare complications including meningitis, acute transverse myelitis, flaccid paralysis and encephalomyelitis may occur. Recently, many EV71 outbreaks with significant mortality in the Asia-Pacific region and beyond have posed serious public health concerns worldwide. Fatal encephalomyelitis is mainly the result of severe inflammation and neuronal damage in the brainstem, spinal cord and other parts of the brain. Medullary involvement is believed to result in neurogenic pulmonary oedema and sudden collapse typically found in fatal cases. A recent study has demonstrated viral replication in tonsillar crypt epithelium, suggesting that tonsil may be a portal for viral entry into the body. Presumably this is followed by viral replication in other sites (e.g. skin) and/or viraemia, leading to neuroinvasion possibly by a retrograde peripheral motor nerve route. There is also increasing evidence that the SCARB2 receptor may be an important receptor for human EV71 infection. A possible hypothesis for viral transmission into the body leading to CNS infection will be discussed. The value of human material and animal models to study viral infections in general and EV71 infection in particular is emphasized.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
PATHOLOGY 2014 ABSTRACT SUPPLEMENT
2. Tanino M, Sasajima T, Nanjo H, et al. Rapid immunohistochemistry based on alternating current electric field for intraoperative diagnosis of brain tumors. Brain Tumor Pathol 2014; May 8: (Epub ahead of print).
Infectious Diseases and Tropical Disease Pathology: SC16-1 NEEDLE IN A HAYSTACK: THE NEW WORLD OF DIAGNOSTICS FOR MICRO-ORGANISMS Danny Arnold Milner Jr Brigham and Womens’ Hospital, Boston, Massachusetts, USA Infectious disease diagnostics from tissue specimens has relied upon either the presence of a tissue reaction specific to an infection type or morphological identification of an organism for the last century or more. Molecular diagnostics (the detection of RNA or DNA) from a micro-organism in a sample offers the promise of ultra-sensitive testing for patient care but requires careful selection and use for each patient. Examples of successful approaches include confirmation of species of mycobacteria in AFB-positive case using consensus primers and sequencing, confirmation of species of fungi in sections showing fungal forms using consensus primers and sequencing, and organism specific confirmatory PCR on suspicious lesions. Similarly, clinical laboratory panels for GI pathogens and respiratory pathogens are growing in popularity for rapid screening and accurate diagnosis across a range of organisms. As with cancer diagnostics, one of the next phases of microorganism detection will be for the expression profile or pattern of specific genes which not only identify the organism but provide information on drug resistance, behavior, prognosis, and treatment. A discussion of how these technologies work in basic science are moving into the forefront of patient care will be presented with examples.
Infectious Diseases and Tropical Disease Pathology: SC16-1 rRNA SEQUENCING IN MOLECULAR MICROBIOLOGICAL DIAGNOSIS OF BACTERIAL INFECTIONS IN THE AUTOPSY SETTING John D. Hart1,2,3, Teresa Street3, John M. Wrightson3, David P. Moore4,5, Anthony G. Scott6, Derrick W. Crook3 and Gareth D. H. Turner7,8,9 1University of Malawi College of Medicine, Mahatma Gandhi Road, Blantyre, Malawi, 2London School of Hygiene and Tropical Medicine, Keppel Street, London, UK, 3Department of Microbiology, Nuffield Department of Medicine, Oxford University, John Radcliffe Hospital, Oxford, UK, 4Faculty of Health Sciences, University of the Witwatersrand, Chris Hani Baragwanath Hospital, Johannesburg, South Africa, 5Department of Paediatrics and Child Health, Metabolic Unit, Chris Hani Baragwanath Hospital, Johannesburg, South Africa, 6KEMRIWellcome Trust Research Programme, Kilifi, Kenya, 7Centre for Tropical Diseases, Nuffield Department of Medicine, Oxford University, John Radcliffe Hospital, Oxford, UK, 8Department of Cellular Pathology, Oxford University, John Radcliffe Hospital, Oxford, UK, and 9Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Pathology (2014), 46(S2)
Diagnosing the aetiology of infectious diseases at autopsy, such as pneumonia, meningitis, sepsis or SUDI, is complicated due to issues including post mortem contamination, difficulty culturing fastidious organisms and subjective interpretation of polymicrobial cultures. Death of organisms may also occur post mortem, especially if antibiotics were given to the patient, but residual DNA from non-viable organisms, amenable to molecular detection, may remain. The 16S rRNA gene is present in all bacteria with conserved and hyper-variable regions along its length, allowing amplification and sequencing of all bacterial 16S sequences present in a sample. 16S sequencing offers potential advantages over culture-based diagnostics and is increasingly used in clinical practice. It has been used to identify bacteria in formalin fixed paraffin embedded (FFPE) surgical pathology specimens but its use has not been reported in autopsy diagnosis. This talk will summarise a study aimed to assess the utility of 16S sequencing as an adjunctive microbiological test in the autopsy. Our preliminary work has used post mortem lung tissue samples from children dying with pneumonia as part of the Pneumonia Etiology Research for Child Health (PERCH) project. The technique has identified known pathogens in some cases and provided additional diagnostic information in others. The presentation will discuss the technical aspects of 16S sequencing from FFPE and autopsy material, and the issues surrounding its application to diagnosis in comparison with standard culture based diagnostics on surgical/autopsy material.
Infectious Diseases and Tropical Disease Pathology: SS16-1 UNDERSTANDING ENTEROVIRUS 71 INFECTION AND NEUROPATHOGENESIS: PERSPECTIVE FROM HUMAN AND ANIMAL MODEL STUDIES Kum Thong Wong1 and Kien Chai ONg2 1Department of Pathology, Faculty of Medicine, University of Malaya, and 2Department of Biomedical Science, Faculty of Medicine, University of Malaya, Malaysia Enterovirus 71 (EV71) (family Picornaviridae, genus Human Enterovirus A) causes the relatively mild hand, foot and mouth disease in children. However, rare complications including meningitis, acute transverse myelitis, flaccid paralysis and encephalomyelitis may occur. Recently, many EV71 outbreaks with significant mortality in the Asia-Pacific region and beyond have posed serious public health concerns worldwide. Fatal encephalomyelitis is mainly the result of severe inflammation and neuronal damage in the brainstem, spinal cord and other parts of the brain. Medullary involvement is believed to result in neurogenic pulmonary oedema and sudden collapse typically found in fatal cases. A recent study has demonstrated viral replication in tonsillar crypt epithelium, suggesting that tonsil may be a portal for viral entry into the body. Presumably this is followed by viral replication in other sites (e.g. skin) and/or viraemia, leading to neuroinvasion possibly by a retrograde peripheral motor nerve route. There is also increasing evidence that the SCARB2 receptor may be an important receptor for human EV71 infection. A possible hypothesis for viral transmission into the body leading to CNS infection will be discussed. The value of human material and animal models to study viral infections in general and EV71 infection in particular is emphasized.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.