RESUMO
Primary graft dysfunction (PGD) is a principal cause of early morbidity and mortality after lung transplantation, but its pathogenic mechanisms are not fully clarified. To date, studies using standard clinical assays have not linked microbial factors to PGD. We previously used comprehensive metagenomic methods to characterize viruses in lung allografts >1 mo after transplant and found that levels of Anellovirus, mainly torque teno viruses (TTVs), were significantly higher than in nontransplanted healthy controls. We used quantitative polymerase chain reaction to analyze TTV and shotgun metagenomics to characterize full viral communities in acellular bronchoalveolar lavage from donor organs and postreperfusion allografts in PGD and non-PGD lung transplant recipient pairs. Unexpectedly, TTV DNA levels were elevated 100-fold in donor lungs compared with healthy adults (p = 0.0026). Although absolute TTV levels did not differ by PGD status, PGD cases showed a smaller increase in TTV levels from before to after transplant than did control recipients (p = 0.041). Metagenomic sequencing revealed mainly TTV and bacteriophages of respiratory tract bacteria, but no viral taxa distinguished PGD cases from controls. These findings suggest that conditions associated with brain death promote TTV replication and that greater immune activation or tissue injury associated with PGD may restrict TTV abundance in the lung.
Assuntos
Rejeição de Enxerto/etiologia , Transplante de Pulmão/efeitos adversos , Metagenômica , Disfunção Primária do Enxerto/etiologia , Sistema Respiratório/virologia , Doadores de Tecidos , Torque teno virus/genética , Adulto , Idoso , Estudos de Casos e Controles , DNA Viral/genética , Feminino , Seguimentos , Genoma Viral , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Disfunção Primária do Enxerto/patologia , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
Few studies have examined the lung virome in health and disease. Outcomes of lung transplantation are known to be influenced by several recognized respiratory viruses, but global understanding of the virome of the transplanted lung is incomplete. To define the DNA virome within the respiratory tract following lung transplantation we carried out metagenomic analysis of allograft bronchoalveolar lavage (BAL), and compared with healthy and HIV+ subjects. Viral concentrates were purified from BAL and analyzed by shotgun DNA sequencing. All of the BAL samples contained reads mapping to anelloviruses, with high proportions in lung transplant samples. Anellovirus populations in transplant recipients were complex, with multiple concurrent variants. Quantitative polymerase chain reaction quantification revealed that anellovirus sequences were 56-fold more abundant in BAL from lung transplant recipients compared with healthy controls or HIV+ subjects (p < 0.0001). Anellovirus sequences were also more abundant in upper respiratory tract specimens from lung transplant recipients than controls (p = 0.006). Comparison to metagenomic data on bacterial populations showed that high anellovirus loads correlated with dysbiotic bacterial communities in allograft BAL (p = 0.008). Thus the respiratory tracts of lung transplant recipients contain high levels and complex populations of anelloviruses, warranting studies of anellovirus lung infection and transplant outcome.
Assuntos
Anelloviridae/genética , Líquido da Lavagem Broncoalveolar/química , Transplante de Pulmão , Metagenômica , Sistema Respiratório/virologia , Anelloviridae/isolamento & purificação , Estudos de Casos e Controles , Biologia Computacional , DNA Viral/genética , Seguimentos , Rejeição de Enxerto/genética , Rejeição de Enxerto/virologia , Sobrevivência de Enxerto , Humanos , Complicações Pós-Operatórias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , TransplantadosRESUMO
Since the initial description in 1993 of hantavirus pulmonary syndrome and its novel aetiological agent, Sin Nombre virus, our knowledge of the epidemiology of New World hantaviruses has continued to evolve. After the identifying outbreak in the southwestern US, four hantaviruses have been identified in North America with specific rodent hosts and associated with a number of sporadic cases. This stability of case recognition in North America is in contrast to the multiple outbreaks and endemic cases in South America. Despite a plethora of New World hantaviruses and new evidence of person-to-person transmission, the ecological and personal determinants of this human infection remain a mystery.
Assuntos
Síndrome Pulmonar por Hantavirus/diagnóstico , Ecologia , Orthohantavírus , Síndrome Pulmonar por Hantavirus/epidemiologia , Síndrome Pulmonar por Hantavirus/transmissão , Humanos , América do Norte/epidemiologia , América do Sul/epidemiologiaRESUMO
Se examina la importancia que para los educadores de salud tienen las observaciones antropologicas al estudiar factores y necesidades culturales en relacion con el diagnostico de enfermedades, su evaluacion y el proceso de decision terapeutica. Se ponen de relieve nuevas tendencias en los modelos de adopcion de decisiones que muestran la logica subyacente a las elecciones em materia de salud