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.

Keywords: Hematopoietic cell transplantation; Lower respiratory tract disease; Parainfluenza virus; Progression; Ribavirin.

Figure 1.. Monthly distribution of PIV infection.

(A) The number of URTI or LRTD cases with PIV infection by month between January 1992 and December 2011. (B) The number of PIV infection cases by each type between January 1992 and December 2011. PCR testing for PIV-4 started in January 2007 and the cases with unknown PIV type were excluded.

Figure 2.. Probability of progression from URTI to LRTD.

(A) The probability of progression from URTI to final LRTD status. Black line, progression from URTI to any type of LRTD; Blue line, progression from URTI to possible LRTD; Red line, progression from URTI to probable LRTD; Green line, progression from URTI to proven LRTD. (B) The probability of progression from URTI or possible LRTD to probable or proven LRTD.

Figure 3.. Probability of progression from URTI/possible LRTD to probable/proven LRTD.

(A) Cumulative incidence of progression by lymphocyte levels. (B) Cumulative incidence of progression by monocyte levels. (C) Cumulative incidence of progression by PIV type. (D) Cumulative incidence of progression to LRTD by steroid dose before diagnosis and PIV type.

Figure 4.. Probability of progression from URTI/possible LRTD to probable/proven LRTD by the number of risk factors.

Cumulative incidence of progression by the number of risk factors (PIV type, co-pathogen, monocyte count, and steroid dose; n=64 in 0, n=227 in 1, n=142 in 2, and n=43 in ≥3 risk factors).

Figure 5.. Probability of overall survival comparing LRTD with and without prior URTI.

Kaplan-Meier estimate of overall survival among 121 probable/proven LRTD cases. (P value 1.00).