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WU polyomaviruses in children with and without lower respiratory tract infection at the pediatric intensive care unit
S12
Oral presentations, ESCV 2009, Amsterdam / Journal of Clinical Virology 44 Suppl. 1 (2008) S5–S16
Session 5. General clinical virology O.5.1 Prevalence of human bocavirus and KI/WU polyomaviruses in children with and without lower respiratory tract infection at the pediatric intensive care unit A.C. van de Pol1 , T.F.W. Wolfs1 , N.J.G. Jansen1 , J.L.L. Kimpen1 , A.M. van Loon1 , J.W.A. Rossen2 . 1 University Medical Center Utrecht, Utrecht, Netherlands, 2 St. Elisabeth Hospital Tilburg, Tilburg, Netherlands Purpose: Little is known about the prevalence of human bocavirus (HBoV), KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) in children with severe lower respiratory tract infections (LRTIs) admitted to the pediatric intensive care unit (PICU). The aim of our study was to evaluate the prevalence of HBoV, KIPyV and WUPyV in PICU patients with and without LRTI. Methods: For the LRTI group PICU patients under five years of age were included during three winters (2005–2008). For the control group PICU patients under 18 years of age admitted for other reasons than LRTI were included during one winter (2005–2006). Respiratory specimens of both groups were tested for HBoV, KIPyV and WUPyV by real-time PCR. Specimens in the LRTI group were also tested by real-time PCR for other respiratory viruses. Results: Respiratory specimens of 78 LRTI patients and 83 controls were examined. HBoV, KIPyV and WUPyV were detected in 4 (5.1%), 0 (0%), and 2 (2.6%) LRTI patients and 4 (4.8%), 4 (4.8%), and 2 (2.4%) controls, respectively. Multiple viruses were present in 3 out of 4 HBoV and 2 out of 2 WUPyV positive LRTI patients. In the LRTI patient with single HBoV infection, the virus was present in very high quantities. Conclusion: In conclusion, at the PICU-population level detection of HBoV, KIPyV, and WUPyV viruses was not associated with lower respiratory tract infection in children admitted to the PICU. In individual patients, however, HBoV may cause LRTI. O.5.2 Correlation between (semi-)quantity of respiratory viruses using a multiple RT-PCR and clinical respiratory symptoms in children under 6 years D. Pajkrt, R.R. Jansen, R. Molenkamp, J. Schinkel. Academic Medical Center, Amsterdam, Amsterdam, Netherlands Purpose: Molecular techniques have increased the sensitivity of diagnosing respiratory viruses. The consequence of increased sensitivity is that the clinical relevance of a positive PCR result is unclear. We hypothesized that the amount of virus present may be indicative of the clinical severity of respiratory tract infections. We carried out a prospective case-control study to investigate the clinical significance of the (semi)-quantitative presence of respiratory viruses in children under 6 years with (cases) and without clinical symptoms (controls) of a respiratory tract infection. Methods: Nasopharyngeal aspirates (NPAs) were tested on boca-, RS-, parainfluenza 1−4, influenza A and B, corona-, hMP-, parecho-, entero-, adeno- and rhinoviruses using a multiplex RT-PCR. Presence and (semi)quantity of the fourteen viruses were correlated with the severity of clinical symptoms of cases and controls. Cp-value (i.e. the first cycle at which the PCR signal becomes positive) was used as a semiquantitative measure. The lower the Cp-value, the more virus present. Results: In 69% of the 84 cases and in 28% of the 88 controls one or more respiratory viruses could be detected. Rhino- and RSV were detected most frequently in resp. 29%, and 13% of the positive cases, and in resp 15% and 4% of the positive controls. In the case subjects, the mean Cp-value was significantly lower than in the controls. Conclusion: The amount of respiratory virus present can be correlated with the severity of clinical symptoms. This can be of help to interpret the clinical relevance of a positive respiratory virus PCR test. O.5.3 Clinical characteristics of infection with the newer human parechoviruses in children K.C. Wolthers1 , D. Pajkrt1 , K.S.M. Benschop1 , B. Westerhuis1 , R. Molenkamp1 , L. Spanjerberg2 . 1 Academic Medical Center, Amsterdam, Netherlands, 2 Ziekenhuis Amstelland, Amstelveen, Netherlands Background: Human parechovirus (HPeV) 1 and 2 have been associated with gastrointestinal or respiratory symptoms in young children. HPeV3 is
associated with neonatal sepsis. Little is known about the pathology of the new HPeV 4−6 in children. Methods: We evaluated the clinical symptoms of children with HPeV in cerebrospinal fluid (CSF) and children identified with an HPeV 4, 5 or 6 infection in faeces by PCR. Data on clinical symptoms were retrospectively documented by questionnaires. Results: HPeV infections of the CNS were found in 2004 (8.2%) and 2006 (5.7%) but were nearly absent in 2005 and 2007 (0.4−0.7%). Mean age of the children was 2 months, and all were diagnosed with fever and signs of neonatal sepsis and/or meningitis. Out of 275 children positive for HPeV in faeces, 21 were positive for HPeV4, 5 for HPeV5 and 5 for HPeV6. The mean age was 11 months. Children presented in 56% with respiratory complaints, of which 19% had an otitis, and in 64% with gastro-intestinal symptoms. Irritability and/or convulsions were reported in 10% of the patients. There was no diagnosis of sepsis. Hospital stay was 4 days for children with HPeV4−6 infection, and 7 days for CNS-infected children, while 55% resp. 82% were given antibiotics for an average of 6 days. Conclusion: The bi-annual HPeV3 is most likely the predominant CNSinfecting strain, and should be considered as an important cause for sepsis/meningitis in infants. Symptomatic HPeV4−6 infections are seen in relative young children and are associated with respiratory and/or gastrointestinal symptoms. O.5.4 Comparison of human parechovirus and enterovirus detection frequencies in central nervous system related disease − identification of a specifically neuropathogenic HPeV type H. Harvala1 , I. Robertson2 , C. McWilliam Leitch2 , T. Chieochansin2 , K. Templeton1 , P. Simmonds2 . 1 Specialist Virology Centre, Edinburgh, United Kingdom, 2 University of Edinburgh, Edinburgh, United Kingdom Human enteroviruses (EVs), and more recently parechoviruses (HPeVs), have been associated with neonatal sepsis and meningitis. We determined the relative importance of EVs and HPeVs in meningitis and neonatal sepsis, and the specific types involved in central nervous system (CNS) related disease. A highly sensitive nested polymerase chain reaction was used to screen 1286 cerebrospinal fluid (CSF) specimens collected between January 2007 and August 2008 in Edinburgh from subjects <3 months to >65 years of age. HPeV and EV types were identified in 70/75 (93%) of screen positive samples by sequencing the partial capsid-encoding region directly from specimens. HPeV was found only in CSF samples from children under three months old. The yearly prevalence of HPeV in this age group varied from 0% in 2007 to 5.9% in 2008. All 11 HPeV positive samples were identified as HPeV3 despite the detection of HPeV1, 3 and 6 in respiratory and faecal samples over the same period. These frequencies approached or exceeded that of EVs (2.4% 2007, 8.1% 2008), although EVs infected a much wider age range. The most prevalent EV types in 2007 were echovirus 9, 30 and 6 accounting for 85% of CNS related infections, but several uncommon serotypes including CAV6 were also detected. EV diversity was greater in 2008. HPeVs and EVs are prevalent and significant CNS related pathogens, infecting especially young children. Typing methods developed here will be of value in further HPeV and EV screening of sepsis and meningitis cases as well as in molecular epidemiological studies. O.5.5 The new Human Theiler’s-like Cardiovirus (HTCV) is a ubiquitous pathogen that is contracted in early childhood S. Erkens-Hulshof1 , G.J. Zoll1 , F. Verduyn-Lunel, J. Bakkers1 , W.J.G. Melchers1 , F.J.M. van Kuppeveld1 , J.M.D. Galama2 . 1 Radboud University Medical Center, Nijmegen, Netherlands, 2 Radboud University Medical Center, Department of Medical Microbiology, Virology, Nijmegen, Netherlands Background: In December 2007 we isolated a virus from stool from a 13 months old child. The virus was characterized as a picornavirus, not being enterovirus, parechovirus or rhinovirus. Sequencing revealed close relationship with the new Human Theiler’s-like Cardiovirus (HTCV) Saffoldvirus [Jones et al JCM 2007;45:2144−50]. Based on these sequences, a second isolate was found, isolated in July 2006 from stool from a 3 year old child. Aim: To fully characterize the two viruses. Furthermore, to scrutinize for the epidemiology and clinical significance of HTCV infection.
Oral presentations, ESCV 2009, Amsterdam / Journal of Clinical Virology 44 Suppl. 1 (2008) S5–S16
Session 5. General clinical virology O.5.1 Prevalence of human bocavirus and KI/WU polyomaviruses in children with and without lower respiratory tract infection at the pediatric intensive care unit A.C. van de Pol1 , T.F.W. Wolfs1 , N.J.G. Jansen1 , J.L.L. Kimpen1 , A.M. van Loon1 , J.W.A. Rossen2 . 1 University Medical Center Utrecht, Utrecht, Netherlands, 2 St. Elisabeth Hospital Tilburg, Tilburg, Netherlands Purpose: Little is known about the prevalence of human bocavirus (HBoV), KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) in children with severe lower respiratory tract infections (LRTIs) admitted to the pediatric intensive care unit (PICU). The aim of our study was to evaluate the prevalence of HBoV, KIPyV and WUPyV in PICU patients with and without LRTI. Methods: For the LRTI group PICU patients under five years of age were included during three winters (2005–2008). For the control group PICU patients under 18 years of age admitted for other reasons than LRTI were included during one winter (2005–2006). Respiratory specimens of both groups were tested for HBoV, KIPyV and WUPyV by real-time PCR. Specimens in the LRTI group were also tested by real-time PCR for other respiratory viruses. Results: Respiratory specimens of 78 LRTI patients and 83 controls were examined. HBoV, KIPyV and WUPyV were detected in 4 (5.1%), 0 (0%), and 2 (2.6%) LRTI patients and 4 (4.8%), 4 (4.8%), and 2 (2.4%) controls, respectively. Multiple viruses were present in 3 out of 4 HBoV and 2 out of 2 WUPyV positive LRTI patients. In the LRTI patient with single HBoV infection, the virus was present in very high quantities. Conclusion: In conclusion, at the PICU-population level detection of HBoV, KIPyV, and WUPyV viruses was not associated with lower respiratory tract infection in children admitted to the PICU. In individual patients, however, HBoV may cause LRTI. O.5.2 Correlation between (semi-)quantity of respiratory viruses using a multiple RT-PCR and clinical respiratory symptoms in children under 6 years D. Pajkrt, R.R. Jansen, R. Molenkamp, J. Schinkel. Academic Medical Center, Amsterdam, Amsterdam, Netherlands Purpose: Molecular techniques have increased the sensitivity of diagnosing respiratory viruses. The consequence of increased sensitivity is that the clinical relevance of a positive PCR result is unclear. We hypothesized that the amount of virus present may be indicative of the clinical severity of respiratory tract infections. We carried out a prospective case-control study to investigate the clinical significance of the (semi)-quantitative presence of respiratory viruses in children under 6 years with (cases) and without clinical symptoms (controls) of a respiratory tract infection. Methods: Nasopharyngeal aspirates (NPAs) were tested on boca-, RS-, parainfluenza 1−4, influenza A and B, corona-, hMP-, parecho-, entero-, adeno- and rhinoviruses using a multiplex RT-PCR. Presence and (semi)quantity of the fourteen viruses were correlated with the severity of clinical symptoms of cases and controls. Cp-value (i.e. the first cycle at which the PCR signal becomes positive) was used as a semiquantitative measure. The lower the Cp-value, the more virus present. Results: In 69% of the 84 cases and in 28% of the 88 controls one or more respiratory viruses could be detected. Rhino- and RSV were detected most frequently in resp. 29%, and 13% of the positive cases, and in resp 15% and 4% of the positive controls. In the case subjects, the mean Cp-value was significantly lower than in the controls. Conclusion: The amount of respiratory virus present can be correlated with the severity of clinical symptoms. This can be of help to interpret the clinical relevance of a positive respiratory virus PCR test. O.5.3 Clinical characteristics of infection with the newer human parechoviruses in children K.C. Wolthers1 , D. Pajkrt1 , K.S.M. Benschop1 , B. Westerhuis1 , R. Molenkamp1 , L. Spanjerberg2 . 1 Academic Medical Center, Amsterdam, Netherlands, 2 Ziekenhuis Amstelland, Amstelveen, Netherlands Background: Human parechovirus (HPeV) 1 and 2 have been associated with gastrointestinal or respiratory symptoms in young children. HPeV3 is
associated with neonatal sepsis. Little is known about the pathology of the new HPeV 4−6 in children. Methods: We evaluated the clinical symptoms of children with HPeV in cerebrospinal fluid (CSF) and children identified with an HPeV 4, 5 or 6 infection in faeces by PCR. Data on clinical symptoms were retrospectively documented by questionnaires. Results: HPeV infections of the CNS were found in 2004 (8.2%) and 2006 (5.7%) but were nearly absent in 2005 and 2007 (0.4−0.7%). Mean age of the children was 2 months, and all were diagnosed with fever and signs of neonatal sepsis and/or meningitis. Out of 275 children positive for HPeV in faeces, 21 were positive for HPeV4, 5 for HPeV5 and 5 for HPeV6. The mean age was 11 months. Children presented in 56% with respiratory complaints, of which 19% had an otitis, and in 64% with gastro-intestinal symptoms. Irritability and/or convulsions were reported in 10% of the patients. There was no diagnosis of sepsis. Hospital stay was 4 days for children with HPeV4−6 infection, and 7 days for CNS-infected children, while 55% resp. 82% were given antibiotics for an average of 6 days. Conclusion: The bi-annual HPeV3 is most likely the predominant CNSinfecting strain, and should be considered as an important cause for sepsis/meningitis in infants. Symptomatic HPeV4−6 infections are seen in relative young children and are associated with respiratory and/or gastrointestinal symptoms. O.5.4 Comparison of human parechovirus and enterovirus detection frequencies in central nervous system related disease − identification of a specifically neuropathogenic HPeV type H. Harvala1 , I. Robertson2 , C. McWilliam Leitch2 , T. Chieochansin2 , K. Templeton1 , P. Simmonds2 . 1 Specialist Virology Centre, Edinburgh, United Kingdom, 2 University of Edinburgh, Edinburgh, United Kingdom Human enteroviruses (EVs), and more recently parechoviruses (HPeVs), have been associated with neonatal sepsis and meningitis. We determined the relative importance of EVs and HPeVs in meningitis and neonatal sepsis, and the specific types involved in central nervous system (CNS) related disease. A highly sensitive nested polymerase chain reaction was used to screen 1286 cerebrospinal fluid (CSF) specimens collected between January 2007 and August 2008 in Edinburgh from subjects <3 months to >65 years of age. HPeV and EV types were identified in 70/75 (93%) of screen positive samples by sequencing the partial capsid-encoding region directly from specimens. HPeV was found only in CSF samples from children under three months old. The yearly prevalence of HPeV in this age group varied from 0% in 2007 to 5.9% in 2008. All 11 HPeV positive samples were identified as HPeV3 despite the detection of HPeV1, 3 and 6 in respiratory and faecal samples over the same period. These frequencies approached or exceeded that of EVs (2.4% 2007, 8.1% 2008), although EVs infected a much wider age range. The most prevalent EV types in 2007 were echovirus 9, 30 and 6 accounting for 85% of CNS related infections, but several uncommon serotypes including CAV6 were also detected. EV diversity was greater in 2008. HPeVs and EVs are prevalent and significant CNS related pathogens, infecting especially young children. Typing methods developed here will be of value in further HPeV and EV screening of sepsis and meningitis cases as well as in molecular epidemiological studies. O.5.5 The new Human Theiler’s-like Cardiovirus (HTCV) is a ubiquitous pathogen that is contracted in early childhood S. Erkens-Hulshof1 , G.J. Zoll1 , F. Verduyn-Lunel, J. Bakkers1 , W.J.G. Melchers1 , F.J.M. van Kuppeveld1 , J.M.D. Galama2 . 1 Radboud University Medical Center, Nijmegen, Netherlands, 2 Radboud University Medical Center, Department of Medical Microbiology, Virology, Nijmegen, Netherlands Background: In December 2007 we isolated a virus from stool from a 13 months old child. The virus was characterized as a picornavirus, not being enterovirus, parechovirus or rhinovirus. Sequencing revealed close relationship with the new Human Theiler’s-like Cardiovirus (HTCV) Saffoldvirus [Jones et al JCM 2007;45:2144−50]. Based on these sequences, a second isolate was found, isolated in July 2006 from stool from a 3 year old child. Aim: To fully characterize the two viruses. Furthermore, to scrutinize for the epidemiology and clinical significance of HTCV infection.