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Absence of human Bocavirus in bronchoalveolar lavage fluid of lung transplant patients
Journal of Clinical Virology 44 (2009) 179–180
Contents lists available at ScienceDirect
Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv
Letter to the Editor Absence of human Bocavirus in bronchoalveolar lavage fluid of lung transplant patients
a r t i c l e
i n f o
Keywords: Human Bocavirus Respiratory infection Immunosuppression Lung transplant
Lower respiratory tract infections (LRTIs) remain one of the most common infectious diseases presentations. Despite extensive investigations, the etiologic agents of LRTIs remain elusive with pathogens identified in approximately 35% of patients including lung transplant recipients.1 Viral pathogens account for 20–30% of identified pathogens of LRTIs.2 The role of human Bocavirus (HBoV), a recently identified parvovirus, in causing infections remains controversial. HBoV has been detected from 1.5% to 19% in children with acute LRTIs, usually in association with other common respiratory pathogens.3 However, in symptomatic children HBoV can be the only virus detected in 5% of cases.4 In adults, limited data suggest much lower HBoV detection rates5,6 with no studies in transplant recipients. We prospectively examined 153 consecutive bronchoalveolar lavage (BAL) samples from 120 patients at St Vincent’s Hospital, Sydney in 2007 (Table 1). Twenty lung transplant recipients had 46 surveillance bronchoscopies (median 2, range 1–4) at day 7, 21, 60 and 1 year; and 40 patients for investigation of lower respiratory symptoms (median time from transplantation 90 days, range 1 day–13 years). Presence of HBoV was examined in all BAL samples after DNA extraction with EZ1 Virus Minikit using the BioRobot EZ1 (Qiagen, according to manufacturer’s instructions) and a PCR protocol, as previously described.7 Bacterial and fungal cultures, viral antigen detection and culture (for respiratory syncytial virus, adenoviruses, influenza 1, 2, 3, and parainfluenza A and B), cytology and histopathology were performed on all samples. Results are summarized in Table 1. No HBoV was detected, including lung transplant recipients. Frequent detection of HBoV in the respiratory, gastrointestinal and plasma3 and the recent documentation of seroconversion of symptomatic children8 suggest a pathogenic role in the pediatric population. In contrast, the role of HBoV in adults remains unclear with minimal HBoV detection rates.6,9 Secondary to their immunosuppression, transplant recipients are at the highest risk of acquiring viral pathogens, which often have insidious presentation and can cause pneumonia with increased mortality;1 disseminated
Abbreviations: LRTIs, lower respiratory tract infections; HBoV, human Bocavirus.
Table 1 Findings of 153 bronchoalveolar lavage (BAL) samples from lung transplant recipients and symptomatic non-transplant patients.
Patients Age (mean, range) Male (%) Reason for bronchoscopy BAL Human Bocavirus Pathogen detected (%) Bacterial Fungal Viral Non-infectious diagnosis (%)
Lung transplant
Non-transplant
53 45.5 (16–72) 36 (67.9) Symptomatic 40 0 25a (62.5) 17 4 4 7d (17.5)
67 57.8 (17–90) 38 (56.7) Symptomatic 67 0 14c (20.9) 8 5 1 14f (20.9)
Surveillance 46 0 7b (15.2) 7 0 0 7e (15.2)
a Includes MRSA (7 cases), Pseudomonas aeruginosa (8), Klebsiella. pneumoniae (1), Mycobacterium avium (1), Aspergillus fumigatus (3), Pneumocystis jirovecii (1), Parainfluenza 1 virus (1), Parainfluenza 3 virus (2), Respiratory Syncytial Virus (1). b Pseudomonas aeruginosa (4), Eschericia coli (2), Haemophilus influenzae (1). c Staphylococcus aureus (2), Streptococcus pneumoniae (1), Haemophilus influenzae (1), Klebsiella. pneumoniae (1), Mycobacterium tuberculosis (2), Mycobacterium avium-intracellulare complex (1), Histoplasma capsulatum (1), Aspergillus fumigatus (3), Paecilomyces spp. (1), Parainfluenza 3 virus (2). d Acute rejection (5), Bronchiolitis obliterans (2). e Early histologic findings of rejection. f Malignancy (12), Interstitial lung disease (2).
HBoV infection in a transplanted child has been reported.10 HBoV DNA was not detected in 86 BAL samples from our lung transplant cohorts; this argues against a role for HBoV as a respiratory pathogen in this – most vulnerable – adult population group. The absence of HBoV in the surveillance BAL samples argues against a role as a bystander in the respiratory tract of adults. Unlike other respiratory viruses, detected in 12% of our symptomatic transplant patients (Table 1), data do not support either a pathogenic role of HBoV or participation as co-pathogen in respiratory infections. In other immunosuppressed hosts data are lacking, with the exception of a single case (1/59, 2%) of HBoV DNA detected in BAL samples of HIV-infected adults.11 In conclusion, our findings argue against the pathogenicity of HBoV in LRTIs of adult lung transplant recipients. Studies on other transplant cohorts, targeting the upper
1386-6532/$ – see front matter. Crown Copyright © 2008 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2008.10.010
180
Letter to the Editor / Journal of Clinical Virology 44 (2009) 179–180
respiratory tract, are required to confirm the role of HBoV in respiratory infections. Conflict of interest No conflicts of interest. Acknowledgment The authors would like to thank A/Prof M. Nissen for providing the HBoV DNA used as positive control. References 1. Kim YJ, Boeckh M, Englund JA. Community respiratory virus infections in immunocompromised patients: hematopoietic stem cell and solid organ transplant recipients, and individuals with human immunodeficiency virus infection. Semin Respir Crit Care Med 2007;28:222–42. 2. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Suppl. 2):S27–72. 3. Schildgen O, Muller A, Allander T, Mackay IM, Volz S, Kupfer B, et al. Human bocavirus: passenger or pathogen in acute respiratory tract infections? Clin Microbiol Rev 2008;21:291–304. 4. Allander T, Jartti T, Gupta S, Niesters HG, Lehtinen P, Osterback R, et al. Human bocavirus and acute wheezing in children. Clin Infect Dis 2007;44:904–10. 5. Manning A, Russell V, Eastick K, Leadbetter GH, Hallam N, Templeton K, et al. Epidemiological profile and clinical associations of human bocavirus and other human parvoviruses. J Infect Dis 2006;194:1283–90. 6. Longtin J, Bastien M, Gilca R, Leblanc E, de Serres G, Bergeron MG, et al. Human bocavirus infections in hospitalized children and adults. Emerg Infect Dis 2008;14:217–21.
7. Sloots TP, McErlean P, Speicher DJ, Arden KE, Nissen MD, Mackay IM. Evidence of human coronavirus HKU1 and human bocavirus in Australian children. J Clin Virol 2006;35:99–102. 8. Kantola K, Hedman L, Allander T, Jartti T, Lehtinen P, Ruuskanen O, et al. Serodiagnosis of human bocavirus infection. Clin Infect Dis 2008;46:540–6. 9. Fry AM, Lu X, Chittaganpitch M, Peret T, Fischer J, Dowell SF, et al. Human bocavirus: a novel parvovirus epidemiologically associated with pneumonia requiring hospitalization in Thailand. J Infect Dis 2007;195:1038–45. 10. Schenk T, Strahm B, Kontny U, Hufnagel M, Neumann-Haefelin D, Falcone V. Disseminated bocavirus infection after stem cell transplant. Emerg Infect Dis 2007;13:1425–7. 11. Garbino J, Inoubli S, Mossdorf E, Weber R, Tamm M, Soccal P, et al. Respiratory viruses in HIV-infected patients with suspected respiratory opportunistic infection. Aids 2008;22:701–5.
Spiros Miyakis a,∗ Sebastiaan J. van Hal a Joel Barratt a,b Damien Stark a Debbie Marriott a Jock Harkness a a Department of Microbiology and Infectious Diseases, St.Vincent’s Hospital, Darlinghurst 2010, Sydney, New South Wales, Australia b The Institute for the Biotechnology of Infectious Diseases (IBID), The University of Technology, Sydney, New South Wales, Australia ∗ Corresponding
author. Tel.: +61 2 8382 9196. fax: +61 2 8382 2989. E-mail address: [email protected] (S. Miyakis) 14 October 2008
Contents lists available at ScienceDirect
Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv
Letter to the Editor Absence of human Bocavirus in bronchoalveolar lavage fluid of lung transplant patients
a r t i c l e
i n f o
Keywords: Human Bocavirus Respiratory infection Immunosuppression Lung transplant
Lower respiratory tract infections (LRTIs) remain one of the most common infectious diseases presentations. Despite extensive investigations, the etiologic agents of LRTIs remain elusive with pathogens identified in approximately 35% of patients including lung transplant recipients.1 Viral pathogens account for 20–30% of identified pathogens of LRTIs.2 The role of human Bocavirus (HBoV), a recently identified parvovirus, in causing infections remains controversial. HBoV has been detected from 1.5% to 19% in children with acute LRTIs, usually in association with other common respiratory pathogens.3 However, in symptomatic children HBoV can be the only virus detected in 5% of cases.4 In adults, limited data suggest much lower HBoV detection rates5,6 with no studies in transplant recipients. We prospectively examined 153 consecutive bronchoalveolar lavage (BAL) samples from 120 patients at St Vincent’s Hospital, Sydney in 2007 (Table 1). Twenty lung transplant recipients had 46 surveillance bronchoscopies (median 2, range 1–4) at day 7, 21, 60 and 1 year; and 40 patients for investigation of lower respiratory symptoms (median time from transplantation 90 days, range 1 day–13 years). Presence of HBoV was examined in all BAL samples after DNA extraction with EZ1 Virus Minikit using the BioRobot EZ1 (Qiagen, according to manufacturer’s instructions) and a PCR protocol, as previously described.7 Bacterial and fungal cultures, viral antigen detection and culture (for respiratory syncytial virus, adenoviruses, influenza 1, 2, 3, and parainfluenza A and B), cytology and histopathology were performed on all samples. Results are summarized in Table 1. No HBoV was detected, including lung transplant recipients. Frequent detection of HBoV in the respiratory, gastrointestinal and plasma3 and the recent documentation of seroconversion of symptomatic children8 suggest a pathogenic role in the pediatric population. In contrast, the role of HBoV in adults remains unclear with minimal HBoV detection rates.6,9 Secondary to their immunosuppression, transplant recipients are at the highest risk of acquiring viral pathogens, which often have insidious presentation and can cause pneumonia with increased mortality;1 disseminated
Abbreviations: LRTIs, lower respiratory tract infections; HBoV, human Bocavirus.
Table 1 Findings of 153 bronchoalveolar lavage (BAL) samples from lung transplant recipients and symptomatic non-transplant patients.
Patients Age (mean, range) Male (%) Reason for bronchoscopy BAL Human Bocavirus Pathogen detected (%) Bacterial Fungal Viral Non-infectious diagnosis (%)
Lung transplant
Non-transplant
53 45.5 (16–72) 36 (67.9) Symptomatic 40 0 25a (62.5) 17 4 4 7d (17.5)
67 57.8 (17–90) 38 (56.7) Symptomatic 67 0 14c (20.9) 8 5 1 14f (20.9)
Surveillance 46 0 7b (15.2) 7 0 0 7e (15.2)
a Includes MRSA (7 cases), Pseudomonas aeruginosa (8), Klebsiella. pneumoniae (1), Mycobacterium avium (1), Aspergillus fumigatus (3), Pneumocystis jirovecii (1), Parainfluenza 1 virus (1), Parainfluenza 3 virus (2), Respiratory Syncytial Virus (1). b Pseudomonas aeruginosa (4), Eschericia coli (2), Haemophilus influenzae (1). c Staphylococcus aureus (2), Streptococcus pneumoniae (1), Haemophilus influenzae (1), Klebsiella. pneumoniae (1), Mycobacterium tuberculosis (2), Mycobacterium avium-intracellulare complex (1), Histoplasma capsulatum (1), Aspergillus fumigatus (3), Paecilomyces spp. (1), Parainfluenza 3 virus (2). d Acute rejection (5), Bronchiolitis obliterans (2). e Early histologic findings of rejection. f Malignancy (12), Interstitial lung disease (2).
HBoV infection in a transplanted child has been reported.10 HBoV DNA was not detected in 86 BAL samples from our lung transplant cohorts; this argues against a role for HBoV as a respiratory pathogen in this – most vulnerable – adult population group. The absence of HBoV in the surveillance BAL samples argues against a role as a bystander in the respiratory tract of adults. Unlike other respiratory viruses, detected in 12% of our symptomatic transplant patients (Table 1), data do not support either a pathogenic role of HBoV or participation as co-pathogen in respiratory infections. In other immunosuppressed hosts data are lacking, with the exception of a single case (1/59, 2%) of HBoV DNA detected in BAL samples of HIV-infected adults.11 In conclusion, our findings argue against the pathogenicity of HBoV in LRTIs of adult lung transplant recipients. Studies on other transplant cohorts, targeting the upper
1386-6532/$ – see front matter. Crown Copyright © 2008 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2008.10.010
180
Letter to the Editor / Journal of Clinical Virology 44 (2009) 179–180
respiratory tract, are required to confirm the role of HBoV in respiratory infections. Conflict of interest No conflicts of interest. Acknowledgment The authors would like to thank A/Prof M. Nissen for providing the HBoV DNA used as positive control. References 1. Kim YJ, Boeckh M, Englund JA. Community respiratory virus infections in immunocompromised patients: hematopoietic stem cell and solid organ transplant recipients, and individuals with human immunodeficiency virus infection. Semin Respir Crit Care Med 2007;28:222–42. 2. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Suppl. 2):S27–72. 3. Schildgen O, Muller A, Allander T, Mackay IM, Volz S, Kupfer B, et al. Human bocavirus: passenger or pathogen in acute respiratory tract infections? Clin Microbiol Rev 2008;21:291–304. 4. Allander T, Jartti T, Gupta S, Niesters HG, Lehtinen P, Osterback R, et al. Human bocavirus and acute wheezing in children. Clin Infect Dis 2007;44:904–10. 5. Manning A, Russell V, Eastick K, Leadbetter GH, Hallam N, Templeton K, et al. Epidemiological profile and clinical associations of human bocavirus and other human parvoviruses. J Infect Dis 2006;194:1283–90. 6. Longtin J, Bastien M, Gilca R, Leblanc E, de Serres G, Bergeron MG, et al. Human bocavirus infections in hospitalized children and adults. Emerg Infect Dis 2008;14:217–21.
7. Sloots TP, McErlean P, Speicher DJ, Arden KE, Nissen MD, Mackay IM. Evidence of human coronavirus HKU1 and human bocavirus in Australian children. J Clin Virol 2006;35:99–102. 8. Kantola K, Hedman L, Allander T, Jartti T, Lehtinen P, Ruuskanen O, et al. Serodiagnosis of human bocavirus infection. Clin Infect Dis 2008;46:540–6. 9. Fry AM, Lu X, Chittaganpitch M, Peret T, Fischer J, Dowell SF, et al. Human bocavirus: a novel parvovirus epidemiologically associated with pneumonia requiring hospitalization in Thailand. J Infect Dis 2007;195:1038–45. 10. Schenk T, Strahm B, Kontny U, Hufnagel M, Neumann-Haefelin D, Falcone V. Disseminated bocavirus infection after stem cell transplant. Emerg Infect Dis 2007;13:1425–7. 11. Garbino J, Inoubli S, Mossdorf E, Weber R, Tamm M, Soccal P, et al. Respiratory viruses in HIV-infected patients with suspected respiratory opportunistic infection. Aids 2008;22:701–5.
Spiros Miyakis a,∗ Sebastiaan J. van Hal a Joel Barratt a,b Damien Stark a Debbie Marriott a Jock Harkness a a Department of Microbiology and Infectious Diseases, St.Vincent’s Hospital, Darlinghurst 2010, Sydney, New South Wales, Australia b The Institute for the Biotechnology of Infectious Diseases (IBID), The University of Technology, Sydney, New South Wales, Australia ∗ Corresponding
author. Tel.: +61 2 8382 9196. fax: +61 2 8382 2989. E-mail address: [email protected] (S. Miyakis) 14 October 2008