Successful Treatment of Parainfluenza Virus Respiratory Tract Infection With DAS181 in 4 Immunocompromised Children

Abstract

BackgroundParainfluenza 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.MethodsPatients 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.ResultsFour 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.ConclusionDAS181 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.

Clinical Pharmacokinetics of Inhaled Antimicrobials

“…high-dose ribavirin and recombinant human catalase) [181,182]. However, a recombinant protein with sialidase activity (DAS181) has been used to treat human parainfluenza virus 3 infection in several small case reports [183][184][185]. Additionally, inhaled cidofovir has been shown to protect against rabbitpox (a member of the same viral family as smallpox) infection in rabbits [186].…”

Meeting report: 4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses

“…More than 80 patients, primarily immunocompromised transplant patients, have been treated with DAS181 on a compassionate use basis. There was a decrease in virus load and less need for oxygenation in four PIV-infected children (Waghmare et al, 2015). A cystic fibrosis patient infected with an oseltamivir-resistant influenza virus showed improvement (Silveira et al, 2015), and hematopoietic cell transplant (HTC) recipients infected with PIV have also appeared to benefit (Chalkias et al, 2014).…”

Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference

“…The replacement of inhaled ribavirin with oral ribavirin is now also being investigated. DAS181, an inhaled sialidase, is undergoing clinical development for the treatment of PIV in adults and children (Russell and Ison, 2017;Waghmare et al, 2015) although there has been some failure reported, due to coinfection with bacteria or fungus.…”