title: Successful Treatment of Parainfluenza Virus Respiratory Tract Infection With DAS181 in 4 Immunocompromised Children.
abstract: BACKGROUND
  Parainfluenza virus (PIV), a common pediatric pathogen, is associated with significant morbidity in immunocompromised (IC) hosts. DAS181, a novel sialidase fusion protein inhibitor, seems to be effective against PIV in vitro and in vivo; its use in IC children has not been evaluated.
  
  
  METHODS
  Patients were diagnosed with PIV infection using a quantitative reverse transcription-polymerase chain reaction. DAS181 was obtained under emergency investigational new drug applications and was administered via aerosol chamber or nebulizer. Patients were assessed daily for their clinical condition and adverse outcomes.
  
  
  RESULTS
  Four pediatric hematopoietic cell transplantation (HCT) patients with PIV detected in respiratory specimens were identified and treated with DAS 181. Patients 1 and 2 were diagnosed with PIV lower respiratory tract infection (LRTI) by bronchoalveolar lavage at 9 months and 2 days after allogeneic transplantation, respectively. Patient 3 was on chemotherapy prior to planned autologous HCT at time of PIV diagnosis from a nasal swab. Patient 4 was diagnosed with PIV via nasal wash 2 days after HCT. Patients 1-3 had clinical symptoms and chest imaging consistent with LRTI. Inhaled DAS181 was administered for 5-10 days. All 4 patients tolerated therapy well. Clinical improvement in oxygen requirement and respiratory rate was observed in all patients who required oxygen at therapy initiation. Viral load decreased in all patients within 1 week of therapy and became undetectable by day 3 of therapy in patient 3.
  
  
  CONCLUSIONS
  DAS181 was used to treat 4 severely IC pediatric patients with PIV disease. The drug was well tolerated. Improvement in both viral loads and symptoms after initiation of therapy was observed in all cases. This report supports prospective, randomized studies in IC patients with PIV infection.
authors.affiliation: Seattle Children's Hospital , Washington ; University of Washington , Seattle ; Fred Hutchinson Cancer Research Center , Seattle, Washington.
authors.forename: Alpana
authors.initials: A
authors.lastname: Waghmare
authors.affiliation: Seattle Children's Hospital , Washington ; University of Washington , Seattle.
authors.forename: Thor
authors.initials: T
authors.lastname: Wagner
authors.affiliation: Seattle Children's Hospital , Washington ; University of Washington , Seattle ; Fred Hutchinson Cancer Research Center , Seattle, Washington.
authors.forename: Robert
authors.initials: R
authors.lastname: Andrews
authors.affiliation: Seattle Children's Hospital , Washington ; University of Washington , Seattle.
authors.forename: Sherilyn
authors.initials: S
authors.lastname: Smith
authors.affiliation: University of Washington , Seattle.
authors.forename: Jane
authors.initials: J
authors.lastname: Kuypers
authors.affiliation: University of Washington , Seattle ; Fred Hutchinson Cancer Research Center , Seattle, Washington.
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.affiliation: Ansun BioPharma, San Diego, California.
authors.forename: Ronald
authors.initials: R
authors.lastname: Moss
authors.affiliation: Seattle Children's Hospital , Washington ; University of Washington , Seattle.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Englund
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D006801:Humans; D016867:Immunocompromised Host / Q000502:physiology*; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000150:complications; D008297:Male; D009447:Neuroblastoma / Q000150:complications; D010223:Parainfluenza Virus 2, Human / Q000187:drug effects* / Q000502:physiology; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects* / Q000502:physiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications; D011446:Prospective Studies; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000188:drug therapy*; D010253:Respirovirus Infections / Q000188:drug therapy*; D019351:Rubulavirus Infections / Q000188:drug therapy*; D016511:Severe Combined Immunodeficiency / Q000150:complications; D014180:Transplantation / Q000009:adverse effects; D019562:Viral Load / Q000187:drug effects / Q000502:physiology
chemical_list: D011993:Recombinant Fusion Proteins; C525612:oplunofusp; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: antiviral therapy; hematopoietic cell transplantation; parainfluenza virus