Community-acquired Respiratory Virus Infections Research Articles

Community-acquired respiratory viral infections in lung transplant recipients

Community-acquired respiratory virus (CARV) infections are a significant cause of morbidity and sometimes mortality in lung transplant recipients (LTRs); this review will focus on the most recent advances in this field. Recent advancements in molecular diagnostics have resulted in the detection of higher rates of CARVs in LTRs. Persistence of rhinovirus has been implicated in the development of acute and chronic rejection, whereas the role of bocavirus remains uncertain. The data on the association of CARV infections with acute or chronic rejection remain less. A recent systematic review failed to show an association between CARV infections and acute or chronic rejection. Different routes of administration of antiviral medications, vaccines and newer promising antiviral medications are being evaluated to assess efficacy and safety. Similarly, newer strategies of vaccination may potentiate the immune response in these patients. With current advanced investigating tools, the full impact of CARV infections in LTR is increasingly coming to realization. Research for novel effective treatments and improved responses to current and new vaccines is ongoing; they would provide great benefit in solving this complex and ever-evolving problem.

Effect of Hypogammaglobulinemia on the Incidence of Community-Acquired Respiratory Viral Infections After Lung Transplantation

BackgroundHypogammaglobulinemia (HGG) has been associated with an increased risk of infectious complications in lung transplant recipients, but its effect specifically on community-acquired respiratory viruses (CARVs) remains unknown. This study aimed to determine if lung transplant recipients with HGG are at an increased risk of developing CARV infection. Secondary endpoints included the effect of HGG on lung function, incidence of rejection, and mortality. MethodsA retrospective review of all lung transplant recipients from 2008 to 2011 was performed. Patients were stratified as either having HGG after transplantation or having normal IgG titers according to their nadir IgG level. HGG was defined a serum IgG level of <700 mg/dL. CARVs included human metapneumovirus, influenza A/B, respiratory syncytial virus A/B, parainfluenza 1/2/3, rhinovirus, and adenovirus isolated from bronchoalveolar lavage/wash, sputum, or nasal swab. ResultsThe cohort consisted of 263 patients with a mean follow-up time of 612 ± 356 days. The incidence of CARV infection was 27% in patients with normal IgG titers and 23.4% in patients with HGG (P = .62). No difference in rejection, mortality, or lung function was found between the groups. As expected, patients who ever had a CARV infection had a significantly lower 1-second forced expiratory volume % reference on their most recent spirometry than those who had not had a CARV infection (81.6% vs 86.9%; P = .027). ConclusionsAlthough CARV infection has been shown to affect lung graft function, these data suggests that HGG is not associated with the incidence of CARV infection.

Rhinovirus and other respiratory viruses exert different effects on lung allograft function that are not mediated through acute rejection

Community acquired respiratory virus (CARV) infections in lung transplant recipients (LTR) have been associated with adverse outcomes, including acute rejection (AR) and decline in allograft function, in some but not in all studies. Spirometry and transbronchial biopsy results of LTR diagnosed with CARV infection over a two-yr period were extracted from clinical records. Primary outcomes, studied at 1-2.5 months postinfection, were as follows: (i) incidence of biopsy-proven AR (grade >A0) and (ii) allograft function, defined by forced expiratory volume in one s (FEV(1)). A reference group of biopsies (n = 526) collected during the study period established the baseline incidence of AR. Rhinovirus (RV) and non-rhinovirus (non-RV) infections were analyzed as subgroups. Eighty-seven cases of CARV infection were identified in 59 subjects. Incidences of AR were similar in the post-CARV and reference groups and did not differ significantly after RV vs. non-RV infection. Allograft function declined significantly after non-RV infection, but not after RV infection. In LTR, CARV infections other than RV are associated with allograft dysfunction at 1-2.5 months after infection. However, CARVs do not appear associated with AR at this time point. The impact of specific CARVs on lung allografts, including the development of chronic allograft rejection, merits further study.

Guidelines for community-acquired respiratory virus infections in leukaemia pts

Guidelines for community-acquired respiratory virus infections in leukaemia pts

Respiratory viral infections post-lung transplantation.

Community-acquired respiratory viruses (CARVs) are common pathogens in lung transplant recipients. Infection due to these viruses is associated with multiple complications including: rhinitis, pharyngitis, bronchitis, pneumonia, respiratory failure and even death. CARVs have also become increasingly recognized as a risk factor for acute rejection (AR) and bronchiolitis obliterans syndrome (BOS). Newer diagnostic techniques have enhanced the accuracy of diagnosis, but proven treatment options for CARVs are limited. Further insight into the immune response and allograft dysfunction associated with CARV infections is needed in order to develop novel management strategies which can reduce the morbidity and mortality caused by these infectious agents.

CXCR3 Chemokine Ligands During Respiratory Viral Infections Predict Lung Allograft Dysfunction

Community-acquired respiratory viruses (CARV) can accelerate the development of lung allograft dysfunction, but the immunologic mechanisms are poorly understood. The chemokine receptor CXCR3 and its chemokine ligands, CXCL9, CXCL10 and CXCL11 have roles in the immune response to viruses and in the pathogenesis of bronchiolitis obliterans syndrome, the predominant manifestation of chronic lung allograft rejection. We explored the impact of CARV infection on CXCR3/ligand biology and explored the use of CXCR3 chemokines as biomarkers for subsequent lung allograft dysfunction. Seventeen lung transplant recipients with CARV infection had bronchoalveolar lavage fluid (BALF) available for analysis. For comparison, we included 34 BALF specimens (2 for each CARV case) that were negative for infection and collected at a duration posttransplant similar to a CARV case. The concentration of each CXCR3 chemokine was increased during CARV infection. Among CARV infected patients, a high BALF concentration of either CXCL10 or CXCL11 was predictive of a greater decline in forced expiratory volume in 1 s, 6 months later. CXCR3 chemokine concentrations provide prognostic information and this may have important implications for the development of novel treatment strategies to modify outcomes after CARV infection.

Invited commentary

Invited commentary

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.

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.

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.

Respiratory Virus Infections After Marrow Transplant: The Fred Hutchinson Cancer Research Center Experience

Respiratory virus infections are becoming increasingly appreciated causes of morbidity and mortality in bone marrow transplant recipients. Fred Hutchinson Cancer Research Center (FHCRC) has had considerable experience with respiratory syncytial virus (RSV), parainfluenza, influenza, and rhinovirus infections in these patients over the past decade. Overall, RSV accounted for the majority of community-acquired respiratory virus infections (35%), followed by parainfluenza virus (30%), rhinovirus (25%), and influenza virus (11%). Pneumonia occurred frequently among those infected with RSV (49%) or parainfluenza (22%) but infrequently among those infected with influenza virus (<10%) or rhinovirus (3%). In one study conducted at FHCRC, intravenous ribavirin was not effective against established RSV pneumonia. In another, ongoing study, however, short-course aerosolized ribavirin appears to reduce progression of upper respiratory tract infection to pneumonia, but further study is needed. Neither strategy had an obvious impact on viral shedding, although persistence of viral shedding did not correlate with either the development or the outcome of pneumonia.