COMMENTARY

Commonly Encountered Respiratory Virus Infections: Update and New Treatments

Shmuel Shoham, MD; Megan K. Morales, MD

Disclosures

November 08, 2016

Parainfluenza: Common and Challenging in Immunocompromised Patients

Posttransplant patient with shortness of breath. A 52-year-old man who underwent a lung transplant several years earlier is admitted to the hospital with shortness of breath and significant decline in respiratory function. CT of the chest shows multifocal ground-glass pulmonary consolidations. PCR of respiratory tract secretions shows the presence of parainfluenza virus 3 (PIV3). The serum beta-glucan level is found to be elevated as well, suggesting coinfection with a filamentous fungus (eg, aspergillosis).

The spectrum of illnesses caused by PIV ranges from mild, self-limited respiratory infections to severe disease. Serotypes 1 and 2 infect the upper airways and are associated with croup. In children and immunocompromised patients, PIV3 may cause lower respiratory tract involvement. In patients with hematologic cancer or BMT, it the second most common virus to cause pneumonia after RSV, and it is associated with significant morbidity and mortality.[26] Patients with coinfections, which are common, and those needing mechanical ventilation are at highest risk for death.[27]

Supportive care is the cornerstone of management. There are no commercially available drugs that are effective for PIV. Ribavirin both with and without IVIG is generally ineffective, although sometimes used in desperation.[27]

DAS181 (Fludase™) is a novel sialidase fusion protein inhibitor effective against PIV when administered via inhalation for 5-10 days. By removing the sialic acid-containing receptors from the respiratory epithelial cells, influenza virus is also prevented from binding, which was the intended use of DAS181 when developed.[28] Several small studies have reported it to be generally well tolerated, but it may cause a transient elevation in the alkaline phosphatase level.[29,30]

A small study of pediatric hematopoietic stem cell transplant patients with PIV infection described the first use of DAS181 in immunocompromised children.[31] Over a 5- to 10-day course of DAS181, all four patients had clinical improvement in oxygen requirements and respiratory rate, as well as decreased viral load within 1 week. Data in adults are similarly scant but hopeful, with published series consisting of one or two patients treated with the drug after an FDA Investigational New Drug application and institutional review board approval.[29,30,32,33,34]

Limited improvement over time. The patient continues to have cough and shortness of breath, and he develops hypoxemia that requires supplemental oxygen. He ultimately improves, but even after 6 months, he does not regain his previous baseline respiratory function.

Seasonal Influenza: Focus on Pregnancy

A pregnant woman comes to urgent care. A 27-year-old, previously well woman who is in the seventh month of an uneventful pregnancy presents to urgent care 36 hours after abrupt onset of fever, fatigue, myalgia, and headache. She has mild breathlessness and a sore throat. Rapid testing is positive for influenza. Influenza A is known to be circulating in her community.

Prompt treatment of influenza is important in pregnant women, because they are more likely to develop severe disease and are at increased risk for early labor.[35,36] Influenza in pregnancy is also associated with increased risk for hospitalization or intensive care unit admission, acute renal failure, and death.[35] This is probably due to immune and physiologic changes, including decreased T-cell immunity, reduced lung volumes, and increased oxygen consumption, all of which peak late in pregnancy. This risk is further increased when additional conditions are present, such as asthma, diabetes, or obesity.[35]

Treatment should be started as early as possible and ideally within 48 hours of symptom onset. However, pregnant women and other high-risk individuals should be treated even if they present later.[35,36,37]

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