Risk Factors for Parainfluenza Virus Lower Respiratory Tract Disease after Hematopoietic Cell Transplantation

Abstract

Parainfluenza virus (PIV) infection can progress from upper respiratory tract infection (URTI) to lower respiratory tract disease (LRTD) in immunocompromised hosts. Risk factors for progression to LRTD and presentation with LRTD without prior URTI are poorly defined. Hematopoietic cell transplant (HCT) recipients with PIV infection were retrospectively analyzed using standardized definitions of LRTD. PIV was detected in 540 HCT recipients; 343 had URTI alone and 197 (36%) had LRTD (possible, 76; probable, 19; proven, 102). Among 476 patients with positive nasopharyngeal samples, the cumulative incidence of progression to probable/proven LRTD by day 40 was 12%, with a median time to progression of 7 days (range, 2 to 40). In multivariable analysis monocytopenia (hazard ratio, 2.22; P = .011), steroid use ≥1mg/kg prior to diagnosis (hazard ratio, 1.89; P = .018), co-pathogen detection in blood (hazard ratio, 3.21; P = .027), and PIV type 3 (hazard ratio, 3.57; P = .032) were associated with increased progression risk. In the absence of all 4 risk factors no patients progressed to LRTD, whereas progression risk increased to>30% if 3 or more risk factors were present. Viral load or ribavirin use appeared to have no effect on progression. Among 121 patients with probable/proven LRTD, 64 (53%) presented LRTD without prior URTI, and decreased lung function before infection and lower respiratory co-pathogens were risk factors for this presentation. Mortality was unaffected by the absence of prior URTI. We conclude that the risk of progression to probable/proven LRTD exceeded 30% with ≥3 risk factors. To detect all cases of LRTD, virologic testing of lower respiratory samples is required regardless of URTI symptoms.

Respiratory Virus Infections of the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient

“…No patients who lacked all of these risk factors progressed to LRTI, whereas the progression risk increased to greater than 30% if 3 or more risk factors were present. 64 The need for mechanical ventilation in those with LRTI was 43% and survival from onset of mechanical ventilation was 23%. Although overall mortality with PIV LRTI is high after transplant, mortality decreases with time from transplant.…”

“…The use of adjuvant steroids is not advised, because high-dose steroids generally are associated with increased risk of progression to LRTI, prolonged viral shedding, and increased mortality. 9,21,45,53,[62][63][64] As such, consideration should be given to decreasing the steroid dose whenever feasible to less than 1 mg per/kg/d.…”

“…12 There is currently no licensed antiviral agent for the treatment of PIV infection. Despite data supporting in vitro PIV activity, numerous retrospective studies have shown lack of benefit of aerosolized or systemic ribavirin, with or without intravenous immunoglobulin (IVIG), in improving outcomes from an established LRTI or in preventing progression from URTI to LRTI 12,14,64 or in decreasing viral shedding. 12 There are few reports of successful treatment of HCT recipients with serious PIV infection with the investigational agent DAS181, [98][99][100] and data from a phase 2 study, including HCT recipients and HM patients, are forthcoming (https://clinicaltrials.gov/ct2/show/ NCT01644877?cond5das181&rank59).…”

Community-Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs

“…There are no approved drugs that have been demonstrated to be active against HPIV clinically. While most studies have failed to demonstrate a clinical benefit, especially for advanced stages (31,162), many clinicians will administer IVIG and, less frequently, oral or aerosolized ribavirin for high-risk patients (5,73) (Table 4) despite lack of evidence for efficacy, especially for lower RTID.…”

Immunodeficiency risk score for prediction of mortality by parainfluenza virus infection in patients with hematologic malignancy

“…Parainfluenza virus (PIV) infection is one of the most common respiratory virus infections and is a significant cause of morbidity and mortality, especially in patients with hematologic malignancy including recipients of hematopoietic stem cell transplantation (HCT) [1][2][3][4][5][6]. Previous studies have identified various risk factors for the progression of PIV infection to pneumonia and attrib-utable mortality in recipients of HCT [7][8][9][10]. In addition, the efficacy of ribavirin (aerosolized, intravenous, or oral) in previous studies showed mixed results [9,[11][12][13][14].…”