Respiratory virus infection among hematopoietic cell transplant recipients: evidence for asymptomatic parainfluenza virus infection

Abstract

The incidence of respiratory virus infection after hematopoietic cell transplantation (HCT) has probably been underestimated with conventional testing methods in symptomatic patients. This prospective study assessed viral infection episodes by testing weekly respiratory samples collected from HCT recipients, with and without symptoms reported by questionnaire, for 100 days after HCT. Samples were tested by culture and direct fluorescent antibody testing for respiratory syncytial virus (RSV), parainfluenza virus (PIV), and influenza A and B, and by quantitative reverse transcription-polymerase chain reaction for RSV, PIV, influenza A and B, and metapneumovirus (MPV). Of 122 patients, 30 (25%) had 32 infection episodes caused by RSV (5), PIV (17), MPV (6), influenza (3), RSV, or influenza (1). PIV, with a cumulative incidence estimate of 17.9%, was the only virus for which asymptomatic infection was detected. Lower virus copy number in patients with no or one symptom compared with 2 or more symptoms was found for all viruses in all patients (P < .001), with PIV infection having a similar virus-specific comparison (P = .004). Subclinical infection with PIV may help explain why infection-control programs that emphasize symptoms are effective against RSV and influenza but often not against PIV.

Figure 1

Cumulative incidences of first infection episodes of PIV, MPV, influenza, and RSV after transplantation in 122 HCT recipients.

Figure 2

Symptoms reported on symptom surveys simultaneous to respiratory samples collected from HCT recipients with infection episodes caused by respiratory viruses after HCT. Proportion of surveys with symptoms reported are shown for weeks in which respiratory samples tested positive for RSV, PIV, MPV, or influenza vs weeks during which samples tested negative for all 4 viruses.

Figure 3

Respiratory virus–specific median viral loads calculated by using the maximum value per infection episode. The x-axis shows the virus responsible (number of infection episodes), and the horizontal bars show the median values.

Figure 4

Quantitative viral load associated with number of symptoms in samples collected during respiratory virus infection episodes after HCT. (A) All samples that tested positive for respiratory viruses (P < .001). (B) Samples that tested positive for PIV (P = .004). The box plot shows the median and 75th and 25th percentiles; whiskers extend to the upper and lower adjacent values.