Community-acquired Respiratory Viruses Research Articles

The Impact of Pandemic Influenza A H1N1 2009 on Australian Lung Transplant Recipients

Influenza A H1N1 2009 led to 189 deaths during the Australian pandemic. Community-acquired respiratory viruses not only can cause prolonged allograft dysfunction in lung transplant recipients but have also been linked to bronchiolitis obliterans syndrome (BOS). We report the impact of the 2009 H1N1 pandemic on Australian lung transplant recipients. An observational study of confirmed H1N1 cases was conducted across five Australian lung transplant programs during the pandemic. An electronic database collected patient demographics, clinical presentation, management and outcomes up to a year follow-up. Twenty-four H1N1 cases (mean age 43 ± 14 years, eight females) were identified, incidence of 3%. Illness severity varied from upper respiratory tract symptoms only in 29% to lung allograft dysfunction (≥10% decline FEV1) in 75% to death in 5 (21%) cases (pre-existing BOS grade 3, n = 4). Treatment with oseltamivir occurred in all but one case confirmed after death, reduced immunosuppression, n = 1, augmented corticosteroid therapy, n = 16, and mechanical/noninvasive ventilation, n = 4. There was BOS grade decline within a year in six cases (32%). In conclusion, Australian lung transplant recipients were variably affected by the H1N1 pandemic mirroring the broader community with significant morbidity and mortality. After initial recovery, a considerable proportion of survivors have demonstrated BOS progression.

Incidence and morbidity of human metapneumovirus and other community-acquired respiratory viruses in lung transplant recipients

A. Weinberg, D.M. Lyu, S. Li, J. Marquesen, M.R. Zamora. Incidence and morbidity of human metapneumovirus and other community‐acquired respiratory viruses in lung transplant recipients Transpl Infect Dis 2010: 12: 330–335. All rights reserved. : To determine the role of human metapneumovirus (HMPV) in respiratory tract infections (RTIs) of lung transplant recipients, 60 patients were prospectively enrolled in this study spanning from September 2005 to November 2007. Community‐acquired respiratory viruses (CARVs) were identified by polymerase chain reaction and tissue culture in respiratory secretions. Of 112 RTIs, 51 were associated with ≥1 CARV, including 7 HMPV, 13 respiratory syncytial virus (RSV), 19 parainfluenza virus 1, 2, or 3 (PIV), 16 influenza A or B (FLU), and 3 human rhinoviruses (HRV). Sixteen CARV‐RTIs had multiple pathogens. While the standard protocol was to admit all paramyxoviral RTIs for inhaled ribavirin, 16% CARV‐RTIs required hospitalization because of the severity of their respiratory compromise, including 25% of HPMV‐single‐agent RTI, 38% of RSV single‐agent RTI, 10% of PIV‐single‐agent RTI, and 19% of multiple‐agent RTIs. None of those with non‐CARV RTIs required hospitalization. The incidence of clinically diagnosed acute graft rejection in the first 2 months after an RTI varied from 0 for single‐agent HRV to 88% for single‐agent RSV (25% for single‐agent HMPV). A new diagnosis of chronic graft rejection in the first year after an RTI was made in approximately 25% of the RTIs and did not significantly vary with the etiologic agent. No deaths occurred during this study. In conclusion, HMPV was associated with 6% of the RTIs in lung transplant recipients and its morbidity was similar to the average moribidity of CARVs.

A Prospective Molecular Surveillance Study Evaluating the Clinical Impact of Community-Acquired Respiratory Viruses in Lung Transplant Recipients

Community-acquired respiratory viral infections (RVIs) are common in lung transplant patients and may be associated with acute rejection and bronchiolitis obliterans syndrome (BOS). The use of sensitive molecular methods that can simultaneously detect a large panel of respiratory viruses may help better define their effects. Lung transplant recipients undergoing serial surveillance and diagnostic bronchoalveolar lavages (BALs) during a period of 3 years were enrolled. BAL samples underwent multiplex testing for a panel of 19 respiratory viral types/subtypes using the Luminex xTAG respiratory virus panel assay. Demographics, symptoms, and forced expiratory volume in 1 sec were prospectively collected for 93 lung transplant recipients enrolled. Mean number of BAL samples was 6.2+/-3.1 per patient. A respiratory virus was isolated in 48 of 93 (51.6%) patients on at least one BAL sample. Of 81 positive samples, the viruses isolated included rhinovirus (n=46), parainfluenza 1 to 4 (n=17), coronavirus (n=11), influenza (n=4), metapneumovirus (n=4), and respiratory syncytial virus (n=2). Biopsy-proven acute rejection (> or =grade 2) or decline in forced expiratory volume in 1 sec > or =20% occurred in 16 of 48 (33.3%) patients within 3 months of RVI when compared with 3 of 45 (6.7%) RVI-negative patients within a comparable time frame (P=0.001). No significant difference was seen in incidence of acute rejection between symptomatic and asymptomatic patients. Biopsy-proven obliterative bronchiolitis or BOS was diagnosed in 10 of 16 (62.5%) patients within 1 year of infection. Community-acquired RVIs are frequently detected in BAL samples from lung transplant patients. In a significant percentage of patients, symptomatic or asymptomatic viral infection is a trigger for acute rejection and obliterative bronchiolitis/BOS.

Chest CT Features of Community-acquired Respiratory Viral Infections in Adult Inpatients With Lower Respiratory Tract Infections

The appearance of respiratory virus infection on thoracic computed tomography (CT) has been described only to a limited extent in the current literature, and viral pneumonias may be under-recognized by radiologists. Our objective was to describe thoracic CT findings in a broad range of adult inpatients with respiratory virus infections. A retrospective analysis of chest CTs was performed on symptomatic adult inpatients presenting with positive nucleic acid-based assays for 1 of 4 common community-acquired respiratory viruses. Forty-two patients with viral respiratory tract infections who underwent chest CT imaging were evaluated. The reviewer was blinded to virus type and patient information. CT findings were compared with CT reports produced at the time of the original study and correlated with clinical outcome measures. Influenza (n=21), adenovirus (n=9), respiratory syncytial virus (n=8), and parainfluenza (n=4) were represented among the cohort. Three patterns of the disease were seen with viral infection: (1) limited infection with normal imaging (21%), (2) bronchitis/bronchiolitis characterized by bronchial wall thickening and tree-in bud opacities (31%), and (3) pneumonia characterized by multifocal consolidation or ground-glass opacities (36%). Viral infection was suggested in only 4/42 (10%) of the original radiology reports, all of which had evidence of bronchitis/bronchiolitis on chest CT. Viral pneumonia, characterized by multifocal ground-glass opacities or multifocal consolidations, was interpreted as aspiration pneumonia or bacterial pneumonia in 15/16 (94%) of the original CT reports. CT scans of the inpatients with community-acquired viral infections most commonly show 1 of 2 patterns: consolidation and ground-glass opacities or bronchial wall thickening and tree-in-bud opacities. It is important that physicians interpreting CTs with multifocal consolidations and/or multifocal ground-glass opacities consider viral pneumonia when these findings are observed and recommend appropriate diagnostic testing when clinically warranted.

Strong Association between Respiratory Viral Infection Early after Hematopoietic Stem Cell Transplantation and the Development of Life-Threatening Acute and Chronic Alloimmune Lung Syndromes

Alloimmune lung syndromes (allo-LS), including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and bronchiolitis obliterans organizing pneumonia, are severe complications after hematopoietic stem cell transplantation (HSCT). In our cohort of 110 pediatric patients, 30 had allo-LS (27.3%), 18 with ideopathic pneumonia syndrome and 12 with bronchiolitis obliterans syndrome. Multivariate analysis showed that respiratory viral infection early after HSCT is an important predictor for the development of allo-LS (P <.0001). This was true for all viruses tested. In multivariate analysis, allo-LS was the only predictor for higher mortality (P = .04). Paradoxically, prolonged administration of immunosuppressive agents because of acute graft-versus-host disease had a protective effect on the development of allo-LS (P = .004). We hypothesize that early infection of the respiratory tract with a common cold virus makes the lungs a target for alloimmunity.

Antiviral Therapy in Patients With Hematologic Malignancies, Transplantation, and Aplastic Anemia

Advances in supportive care over the past two decades have decreased the morbidity and mortality attributed to opportunistic infections in immunocompromised patients, including those with hematologic malignancies, hematopoietic stem cell transplantation (HSCT), and aplastic anemia. Despite advances in antiviral therapy, opportunistic viral infections such as influenza, herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) still cause significant morbidity and mortality in patients with compromised host defenses. Antiviral agents are key antimicrobials used for treatment and prophylaxis of viral infections in immunocompromised hosts. Currently, there are more than 40 antiviral agents approved for clinical use, but the majority of these agents are for the treatment of human immunodeficiency virus (HIV) or viral hepatitis. This review will focus on antiviral agents used for the treatment of herpesviruses (HSV, VZV, CMV), community-acquired respiratory viruses (influenza), and adenoviruses. Antiviral agents used for the treatment of HIV and viral hepatitis will not be addressed in this review.

Community-Acquired Respiratory Viral Infections in Lung Transplant Recipients: A Single Season Cohort Study

The impact of community-acquired respiratory virus (CARV) infections on bronchiolitis obliterans syndrome (BOS) and outcome after lung transplantation (LTx) and diagnostic techniques were prospectively evaluated. A single-center prospective cohort study was performed in LTx-outpatients between October 31, 2005 and April 30, 2006. Symptoms of respiratory tract infections were recorded and nasopharyngeal and oropharyngeal swabs were obtained. Lower respiratory sampling was performed when indicated. Immunofluorescence testing, cultures, and polymerase chain reaction for 12 different CARV were applied. Patients were followed up until December 31, 2007. New onset and BOS-stage was recorded 1 year after presentation. Three hundred eighty-eight LTx-recipients were screened. Fifty-one percent reported of symptoms of respiratory tract infection. Seven hundred seventy upper and 180 lower respiratory samples were obtained. Thirty-four CARV were detected in 30 patients (7.7%): 12 parainfluenza, 7 respiratory syncytial virus, 6 metapneumovirus, 5 coronavirus, 3 rhinovirus, and 1 influenza virus. At 1 year, 43 new cases of BOS developed. One-year incidence of BOS was 25.0% in CARV-positive versus 9.0% in CARV-negative patients (log-rank P=0.01). Symptomatic CARV-infection proved to be a significant covariate for 1-year BOS-free survival in multivariate analysis (P=0.002, adjusted hazard ratio 4.13). CARV-infection did not influence BOS progression in 88 patients with prior BOS (P 0.45). After paramyxovirus infection, 8 of 24 patients developed new-onset BOS, whereas no case was recorded after rhinovirus and coronavirus infection. Surveillance detected CARV in LTx outpatients infrequently. Symptomatic CARV-infection increases the risk for new onset of BOS, but not progression. Risk to develop BOS was especially increased after paramyxovirus infection.

Infections Relevant to Lung Transplantation

Allograft infection after lung transplantation has a significant impact on the outcome and can be a diagnostic challenge. The increased susceptibility of the pulmonary allograft to infection is due to its direct contact with environmental microbes by inhalation, concurrent immunosuppression, and the impaired clearance mechanisms after denervation of the transplanted lung. The possible spectrum of microorganisms infecting the allograft after lung transplantation is broad, but commonly includes Pseudomonas aeruginosa, cytomegalovirus, community-acquired respiratory viruses, and Aspergillus species. Prophylactic antimicrobial treatment regimens after surgery reduced the incidence of infections. However, preventive strategies for reducing infectious complications used by different transplant centers are still heterogeneous, and many questions regarding efficacy remain unanswered.

Diagnosis and prevention of infection in lung transplantation

The lung is unique amongst solid organ transplants (SOT) for its extreme exposure to the ambient environment which leads to increased vulnerability to infection, particularly when host immune response and barrier mucosal function are impaired. Moreover, resident viruses and other microbes are invariably transplanted within the donor lung(s) which may lead to primary infection within the naive recipient. Importantly, lung allograft infection promotes both innate and adaptive immune responses with resultant chronic allograft dysfunction manifest as bronchiolitis obliterans syndrome (BOS). Infection is both a promoter and result of airway damage, particularly where mucociliary clearance is impaired. The diagnosis and prevention of infection after LTX begins with a comprehensive microbiological survey of the recipient and the potential donor to identify tolerable risks. Prophylactic therapies against identified risks as well as common important infections including herpesgroup viruses, Pneumocystis carinii pneumonia (PCP), Chlamydia species and fungi are commenced routinely with bronchoscopic graft surveillance to identify infections not diagnosed by less invasive means. While effective preventative strategies for cytomegalovirus (CMV) are now readily available, the relative importance of community acquired respiratory viruses (CARV) has increased, especially as diagnosis may be delayed by late presentation and therapies are limited in efficacy. Prevention of CARV remains a challenge.

Detection of multiple respiratory viruses by real-time polymerase chain reaction in infants attending an outpatient clinic

The detection of respiratory viruses in many prospective clinical studies has relied upon detection with standard laboratory assays, such as antigen detection, viral culture, or serology. Data describing the relative importance of community-acquired respiratory viruses, such as rhinovirus, human metapneumovirus (HMPV) [1], and newly described human coronavirus (HCV) subtypes [2], which are not detectable by these standard assays, in healthy young children who are not admitted to the hospital is limited. We developed a novel respiratory real-time reverse transcription (RT) polymerase chain reaction (PCR) panel to detect the presence of HMPV, respiratory syncytial virus (RSV), influenza viruses A and B, parainfluenza virus (PIV) 1, 2, and 3, adenovirus, human coronaviruses Group 1 (229E and NL63) and Group 2 (OC43 and HKU1), and rhinovirus. We conducted a one-year prospective outpatient community-based study of respiratory tract infections (RTIs) in a healthy infant cohort. Our goals were to determine the proportion of viral RTIs caused by these 13 viruses in symptomatic but otherwise healthy infants, as well as to characterize the clinical features of the identified viral infections and quantify the decline in viral load of patients infected with HMPV in this outpatient population. This cohort surveillance study in a population of healthy infants followed for 13 months was conducted between 1 April 2004 and 1 May 2005. Infants between the ages of 0– 6 months were enrolled from the Well Child Clinic at the Madigan Army Medical Center (MAMC) in Tacoma, WA. All subjects were evaluated at each RTI visit by one of three study physicians. Infections were determined to be lower RTIs if bronchiolitis or pneumonia were diagnosed clinically or radiographically by a study physician. We also assessed the presence of a secondary infection requiring antibiotics. During the 13 months of the study, parents called for an appointment in our study clinic if their infant had any respiratory tract symptoms. The clinical data obtained at the study visits for RTIs and by phone follow-up included the duration and complications of the illness, and missed days of work or daycare. Those infants with new onset of at least 2 of 5 respiratory tract symptoms (cough, rhinorrhea, wheezing, fever, and nasal congestion) had a physical Eur J Clin Microbiol Infect Dis (2008) 27:1245–1248 DOI 10.1007/s10096-008-0558-7

Invited commentary

Invited commentary

Major Complications following Hematopoietic Stem Cell Transplantation

Tens of thousands of patients undergo hematopoietic stem cell transplantation (HSCT) annually, 15 to 40% of whom are admitted to the intensive care unit. Pulmonary complications are the most life threatening conditions that develop in HSCT recipients. Both infectious and noninfectious complications occur more frequently in allogeneic HSCT. The management of HSCT recipients requires knowledge of their immune status, appropriate diagnostic evaluation, and early treatment. During the pre-engraftment phase (0 to 30 days after transplant), the most prevalent pathogens causing infection are bacteria and Candida species and, if the neutropenia persists, Aspergillus species. The early post-engraftment phase (30 to 100 days) is characterized by cytomegalovirus (CMV), Pneumocystis jiroveci, and Aspergillus infections. During the late posttransplant phase (> 100 days), allogeneic HSCT recipients are at risk for CMV, community-acquired respiratory virus, and encapsulated bacterial infections. Antigen and polymerase chain reaction assays are important for the diagnosis of CMV and Aspergillus infections. Diffuse alveolar hemorrhage (DAH) and peri-engraftment respiratory distress syndrome occur in both allogeneic and autologous HSCT recipients, usually during the first 30 days. Bronchiolitis obliterans occurs exclusively in allogeneic HSCT recipients with graft versus host disease. Idiopathic pneumonia syndrome occurs at any time following transplant. Bronchoscopy is usually helpful for the diagnosis of the infectious pulmonary complications and DAH.

Influenza Infections after Hematopoietic Stem Cell Transplantation: Risk Factors, Mortality, and the Effect of Antiviral Therapy

Community-acquired respiratory viruses, such as influenza virus, are thought to be major causes of morbidity and mortality in patients who had undergone hematopoietic stem cell transplantation (HSCT). Risk factors for acquisition, progression to pneumonia, and the effect of antiviral therapy are unknown. We reviewed records from patients with documented influenza over 12 consecutive respiratory-virus infection seasons at a single transplantation center. From 1 September 1989 through 31 March 2002, influenza virus was isolated from 62 of 4797 persons undergoing HSCT (1.3%); 44 patients had upper respiratory tract infections (URIs) alone, and 18 developed pneumonia. Among patients with influenza virus infection, pneumonia developed more commonly among those infected earlier after transplantation (median, 36 vs. 61 days, P=.04) and those with concurrent lymphopenia. Of the 51 cases that were initially diagnosed as URIs, 17 were treated with antivirals, and 34 were not treated. Six untreated patients (18%) developed pneumonia, whereas 1 (13%) of 8 patients treated with rimantadine and 0 of 9 treated with oseltamivir developed pneumonia. The duration of influenza virus shedding was longer in patients treated with steroid doses of >1 mg/kg than among those treated with doses of <1 mg/kg (mean, 15 vs. 9 days); there was a trend towards decreased shedding with oseltamivir therapy (but not rimantadine therapy) after controlling for steroid use (P<.08). The 30-day mortality rate was highest among patients who had progression to pneumonia (5 [28%] of 18 patients); pulmonary copathogens (such as Aspergillus fumigatus) were commonly isolated. Influenza virus infection is an important cause of mortality early after HSCT. Our nonrandomized data suggest that early antiviral therapy with neuraminidase inhibitors may prevent progression to pneumonia and decrease viral shedding, which may prevent both influenza-related death in index patients and nosocomial transmission to others.

Community-acquired respiratory viruses

Community-acquired respiratory viruses

Supportive Care

To optimize treatment outcomes for hematologic malignancies, minimizing the consequences of treatment complications requires as much skill as the choice of the treatment itself. Myelosuppression and immunosuppression are frequent complications and have potentially serious infectious consequences. Invasive fungal infections and infections from respiratory viruses are increasing in frequency and have life-threatening potential. Damage to vital organs, especially the liver, is another important concern. In this chapter, the scope of invasive fungal and respiratory viral infections, recent insights into the pathogenesis of hepatic sinusoidal injury, and recent developments that impact prevention and treatment approaches for these complications are described. In Section I, Dr. John Wingard describes the advantages and disadvantages of various treatment options for invasive infections by the two chief fungal pathogens, Candida and Aspergillus. Adjunctive therapies and practical considerations that clinicians should weigh in choosing one or another of the various agents are discussed. The studies that have evaluated antifungal prophylaxis and empirical treatment strategies are reviewed. Finally, new approaches such as combination therapy, new diagnostics, and efforts to bolster host immunity are considered. In Section II, Dr. W. Garrett Nichols describes the epidemiology of community-acquired respiratory viruses (CRV) in patients with hematologic malignancies. Risk factors, clinical syndromes, and possible indirect effects of CRV infections are discussed. Treatment and prevention options are reviewed. In Section III, Dr. George McDonald describes sinusoidal obstruction syndrome (once known as hepatic veno-occlusive disease). Recent insights into pathogenesis are described. Diagnostic criteria and the advantages and disadvantages of various diagnostic methods are reviewed and prognosis is considered. Prevention and treatment options are discussed.

Active surveillance for respiratory virus infections in adults who have undergone bone marrow and peripheral blood stem cell transplantation

Community-acquired respiratory virus (RV) infections are an important cause of disease in immunocompromised adults with cancer. To investigate the viral etiology, incidence, clinical presentation, and outcome of RV infections in an outpatient cohort of adult bone marrow or peripheral blood stem cell transplant (SCT) recipients, we monitored 62 outpatient volunteers from January 1 to April 30, 2001. A nasopharyngeal aspirate was collected from subjects when they reported new respiratory symptoms and tested for RV (influenza A, influenza B, human parainfluenza 1-3, adenovirus, and respiratory syncytial virus) by culture and reverse transcription polymerase chain reaction (RT-PCR) assay. Of 62 subjects enrolled, 27% had received allogeneic SCT and 45% were within 1 year of their transplant. In all, 35 participants (56%) reported 37 episodes of respiratory symptoms. Of the 37 specimens tested, five (14%) were positive for RV by culture and 20 (54%) were positive by RT-PCR. Only six patients with RV infections developed lower respiratory tract illnesses; these patients had received either autologous or allogeneic transplants and developed illnesses between 41 and 2666 days post transplant. Although RV infections were common in SCT outpatients during the RV season, most participants had upper respiratory tract infections, which resolved without the need for hospitalization.

Comparison of conventional viral cultures with direct fluorescent antibody stains for diagnosis of community-acquired respiratory virus infections in hospitalized children.

Because of the widespread availability of rapid viral antigen testing, many institutions never adopted a routine practice of ordering viral cultures to detect community-acquired respiratory viruses (CRVs). The ease of performing complete viral studies in our on site laboratory allowed us to assess the clinical implications of the absence of conventional culture results in previously healthy hospitalized children with CRV infections. From June 1997 through May 2000, the results of direct immunofluorescence assay (DFA) of 1069 nasopharyngeal swab (NP) specimens were compared with simultaneously inoculated conventional tube cell cultures for detection of CRVs. In addition the medical records of 140 previously healthy infants and children hospitalized for management of lower respiratory tract infections caused by culture-proved CRVs were reviewed. Viruses were isolated or detected by DFA or viral culture or both in 468 (30%) of the 1557 NP samples evaluated. The most common CRV isolated was respiratory syncytial virus (49%), followed by parainfluenza viruses (15%), influenza A viruses (14%), rhinoviruses (8%), adenoviruses (4%), enteroviruses (4%) and influenza B viruses (1%). Of the 1069 NP specimens for which both viral culture and rapid antigen testing were performed, 190 specimens were DFA-positive and culture-positive, 7 specimens were DFA-positive and culture-negative, 35 specimens were DFA-negative and culture-positive and 837 specimens were DFA-negative and culture-negative. The overall sensitivity, specificity, positive predictive value and negative predictive value of DFA were 84, 99, 96 and 96%, respectively. Of the 140 hospitalized patients with culture-proved viral cultures (89 respiratory syncytial virus, 22 influenza A, 20 parainfluenza virus and 9 adenovirus), the mean duration of hospital stay was 3.6 days, and the mean time for viral cultures to become positive was 7.7 days (P < 0.001, signed rank test). One hundred twenty (86%) viral cultures did not become positive until after the patient had been discharged from the hospital. In no case was the clinical decision regarding the patient's treatment or discharge from the hospital based on the results of viral culture. We conclude that positive viral cultures have no impact on clinical decision making and management of healthy children during hospitalization for illness attributable to community-acquired respiratory viruses.

Diagnosis and epidemiology of community-acquired respiratory virus infections in the immunocompromised host.

Infections due to community-acquired respiratory viruses are important causes of morbidity and mortality among immunocompromised patients. Respiratory syncytial virus, influenza viruses, and parainfluenza viruses are the most frequent causes of serious lower respiratory tract infections in this patient population. Early diagnosis, often possible with the use of rapid detection assays, is essential for optimal management and prevention of the spread of these serious infections to other vulnerable patients.

Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell transplantation: the Fred Hutchinson Cancer Research Center experience.

Community respiratory viruses (CRVs) are an important cause of morbidity and mortality among recipients of hematopoietic stem cell transplants (HSCT). At the Fred Hutchinson Cancer Research Center, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) infections in HSCT recipients have been studied intensively for more than a decade. Over time, mortality from these infections has declined as the approach to diagnosis has become more aggressive and more stringent preventive measures have been instituted. However, mortality among HSCT recipients with RSV or PIV pneumonia remains high. Uncontrolled studies at our center suggest that prompt therapy with aerosolized ribavirin has reduced mortality from RSV pneumonia but does not appear to affect the course of established PIV pneumonia. Two controlled clinical trials of ribavirin therapy for RSV infection in HSCT recipients are in progress.

Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

Community-acquired respiratory virus infections are a cause of mortality after stem cell transplantation (SCT). A prospective study was performed at 37 centers to determine their frequency and importance. Additional cases were also collected to allow the analysis of risk factors for severe infection. Forty episodes were collected in the prospective study and 53 additional episodes through subsequent case collection. The frequency of documented respiratory virus infections was 3.5% among 819 allogeneic and 0.4% among 1154 autologous SCT patients transplanted during the study period. The frequency of lower respiratory tract infections (LRTI) was 2.1% among allogeneic and 0.2% among autologous SCT patients. The mortality within 28 days from diagnosis of a respiratory viral infection was 1.1% among allogeneic SCT while no autologous SCT patient died. The deaths of five patients (0.6%) were directly attributed to a respiratory virus infection (three RSV; two influenza A). On multivariate analysis, lymphocytopenia increased the risk for LRTI (P = 0.008). Lymphocytopenia was also a significant risk factor for LRTI in patients with RSV infections. The overall mortality in RSV infection was 30.4% and the direct RSV-associated mortality was 17.4%. For influenza A virus infection, the corresponding percentages were 23.0% and 15.3%. This prospective study supports the fact that community-acquired respiratory virus infections cause transplant-related mortality after SCT.