766. Successful Treatment with DAS181 of a Dual Infection with Parainfluenza Virus Type 3 and Influenza A H1N1 Virus in a Lung Transplant Patient
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
Background: Parainfluenza (PIV) and influenza virus infections can both cause severe disease and significant morbidity in hematopoietic and solid organ transplant patients. DAS181 is a recombinant fusion protein containing a sialidase catalytic domain and a respiratory epithelium-anchoring domain. DAS181 exerts an antiviral effect via its sialidase activity, which can cleave sialic acid receptors that are preferentially recognized by influenza strains and parainfluenza strains. DAS181 potently inhibits infection of seasonal influenza strains, including H1N1 strains and neuraminidase-resistant strains. It similarly inhibits PIV infection. 

Methods: A 63 year old lung transplant recipient was diagnosed with PIV-1 and was admitted to the hospital with worsening respiratory status —requiring transfer to the ICU with progressive hypoxic respiratory failure.  She was intubated and placed on mechanical ventilation and multiple bilateral patchy opacities were observed following chest X-ray. In addition to PIV, she was demonstrated to be positive for H1N1 influenza by bronchoalveolar lavage. In light of continued severe disease in spite of initiation of oseltamivir therapy, DAS181 therapy was commenced on a compassionate use basis and viral load and clinical response to treatment were monitored.

Results: Over a five-day course of therapy, O2 requirement was reduced and the patient's respiratory status improved. Extubation occurred on day 5. Viral RNA was serially quantified by reverse-transcriptase PCR. Between day 2 and day 4 of dosing, there was a 60-fold reduction in influenza viral load in the patient's tracheal aspirates. During this same time frame, there was a 7-fold reduction in PIV RNA viral load. NP swabs were negative for both viruses following extubation. The patient tolerated DAS181 well with no signs of significant systemic toxicity.

Conclusion: DAS181 was an effective antiviral in the setting of dual infection with two viruses, PIV and influenza A (H1N1), in a lung transplant recipient with life-threatening lower respiratory tract disease. Viral loads were reduced substantially within 48 hours of treatment, and infection cleared at the end of a treatment course. Respiratory virus co-infections in transplant patients may be well-suited to DAS181 treatment, which merits further study in this high-risk population.

Mark R. Schleiss, MD, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, Emily Schaaf, MD, Pediatric Infectious Diseases, University of Minnesota, Minneapolis, MN, Ronald Moss, MD, Ansun Biopharma, San Diego, CA and Rebecca Routh, PhD, Ansun Pharmaceuticals, San Diego, CA

Disclosures:

M. R. Schleiss, Ansun: Grant Investigator , Research support

E. Schaaf, None

R. Moss, Ansun: Employee , Salary

R. Routh, Ansun: Employee , Salary

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.