Vaccine and Infectious Disease Division

Why are mortality rates for parainfluenza virus-related pulmonary disease so variable?

After hematopoietic cell transplant (HCT) the body’s immune system is severely compromised. As a result, these patients are especially vulnerable to infectious diseases. Infections for which immunocompetent persons can normally mount a sufficient immune response become potentially very serious. One such pathogen HCT recipients are vulnerable to is parainfluenza virus (PIV), which can precipitate lower respiratory tract disease (LRTD), a condition that can often be fatal.

LRTD mortality

Reported mortality rates from LRTD range from 13% to 63%, although the cause for this variability remains a mystery. VIDD scientists set out to delineate the reasons behind such inconsistency. The study, carried out by VIDD Research Associate Sachiko Seo, Affiliate Investigator Angela Campbell, Affiliate Staff Scientist Jane Kuypers, Affiliate Investigator Janet Englund, and Member Michael Boeckh, included 544 individuals who had undergone HCT at the Fred Hutch between 1990 and 2011 and had confirmed PIV infection. This retrospective cohort study evaluated clinical course and survival rates of patients with LRTD, which the investigators separated into 3 categories based on clinical manifestation at diagnosis: ‘Possible,’ ‘Probable’ and ‘Proven’ LRTD. They also compared these patients to those with the less severe PIV disease upper respiratory tract illness (URTI).

The overall survival rates over 90 days for patients with URTI and LRTD were 91% and 62%, respectively
(P < .001) (Figure, top graph). When the authors categorized LRTD into Possible, Probable or Proven, they uncovered drastic differences in disease morbidity and mortality. The survival rates for Possible, Probable and Proven LRTD were 87%, 58% and 45%, respectively        (P < .001) (Figure, bottom graph). This means Proven LRTD was almost twice as deadly when compared to Possible LRTD. A similar trend was seen when looking specifically at predicted pulmonary death by day 90 post PIV infection, as the likelihood was approximately 30% for total LRTD; 10-fold higher than for URTI (3%). Again, splitting LRTD into the three groupings showed a range of fatality rates from approximately 6% (Possible) to 44% (Proven). 

To date, it is not standard practice to clinically diagnose LRTD patients to one of these 3 categories. This study exemplifies the need to delineate LRTD into subgroups for proper diagnosis of and treatment for this disease as well as inform clinical studies of the epidemiology and clinical trials investigating new treatments for PIV.

 


Seo, S, Xie H, Campbell AP, Kuypers JM, Leisenring WM, Englund JA, Boeckh M. Parainfluenza Virus Lower Respiratory Tract Disease after Hematopoietic Cell Transplantation: Viral Detection in the Lung Predicts Outcome. Clin Infect Dis. Apr 2014.
Full-text Article:  http://scholars.fhcrc.org/3460/
PubMed Record: http://www.ncbi.nlm.nih.gov/pubmed/24599766?otool=fhcrclib

 

 

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