Parainfluenza Virus Infections in Patients with Hematologic Malignancies or Following Stem Cell Transplantation: Analysis of Clinical Characteristics, Nosocomial Transmission and Prolonged Viral Shedding

Introduction: Parainfluenza virus (PIV) often causes self-limiting upper respiratory tract infection (URTI) in the immunocompetent host, but can result in severe and even life-threatening lower respiratory tract infection (LRTI) in patients with hematologic malignancies or following stem cell transplantation. In contrast to respiratory syncytial virus or seasonal influenza, PIV is transmitted all year round. Here we analyze clinical characteristics of PIV infection in immunocompromised patients, assess possible risk factors for severe infection and report on nosocomial transmission as well as prolonged viral shedding.

Methods: From July 2013 to June 2016, 108 cases of PIV infection in patients with hematologic malignancies or following stem cell transplantation were identified at our institution. Diagnosis of PIV was done by PCR detection of viral RNA in respiratory materials (nasopharyngeal swabs or bronchoalveolar lavage). Clinical characteristics and outcome of infected patients were retrospectively evaluated. Nosocomial transmission was assumed in patients with detection of PIV ≥ 7 days after hospital admission. The impact of possible influence factors on morbidity and mortality was analyzed by Fisher's exact test. In patients with availability of consecutive tests for PIV, duration of viral shedding was assessed.

Results: 108 patients were identified, 92 with PIV type 1/3, 16 with PIV type 2/4. Median age was 59 years [range 26-79], 64% were male. 75 patients had received a stem cell transplantation (36 allogeneic, 34 autologous, 5 both), 25 of them developed PIV infection before hematologic reconstitution. Nosocomial transmission was apparent in 44% of patients. Regarding outcome, 61 patients had URTI only, 47 patients (44%) developed a LRTI. A severe LRTI, defined as treatment on the intensive care unit and/or death, was present in 10 patients. Of these, 9 patients died, resulting in a mortality rate of PIV associated LRTI of 19%; 1 patient was put on extracorporeal membrane oxygenation and subsequently recovered. Neither type of PIV, underlying hematologic disease or transplant status had a significant impact on outcome. Severe leukopenia (p=0.006), uncontrolled hematologic disease (p=0.007), presence of co-infections (p=0.001) and nosocomial transmission (p<0.001) were significantly associated with an increased risk of developing PIV related LRTI. Presence of respiratory co-infections was a significant risk factor for severe LRTI (p=0.004). Data on duration of viral shedding was available in 40 patients. Median duration of viral shedding was 14 days, but shedding of up to 79 days was observed. Significant risk factors for prolonged viral shedding were severe leukopenia (p=0.02), LRTI (p=0.002), and nosocomial transmission (p=0.007). While PIV infection had no impact on duration until hematologic reconstitution following transplantation, PIV infection prior to hematologic reconstitution following allogeneic transplantation was significantly associated with prolonged viral shedding (p=0.02).

Conclusions: PIV infection can cause significant morbidity and mortality in patients with hematologic malignancies and following stem cell transplantation. Despite thorough hygienic measures, nosocomial transmission was observed in many cases and was associated with an increased risk of developing PIV related LRTI. Prolonged viral shedding of up to 79 days was detected, especially in patients with LRTI, which might facilitate nosocomial spread of PIV and should be taken into account in infection control management.