Marinez, Javier MD; Vincent, Albert L. PhD; Sandin, Ramon L. MD, MS, FCAP; Greene, John N. MD
Division of Infectious Diseases, College of Medicine, University of South Florida, Tampa, FL.
Address correspondence and reprint requests to Javier Marinez, MD, Hidalgo Medical Services, 530 DeMoss St, Lordsburg, NM 88045. E-mail: firstname.lastname@example.org.
Parainfluenza virus (PIV) infection can be a devastating disease in the immunocompromised patient. We describe a case of PIV pneumonia in a patient with a hematologic malignancy who failed rivabirin and intravenous immunoglobulin therapy but whose oxygen requirements and radiological picture improved on interferon alfa-2b. The viral respiratory culture reverted to negative. This successful mode of therapy for PIV infection has not previously been reported.
Human parainfluenza virus (PIV), a member of the Paramyxoviridae family is a common cause of respiratory tract disease. Although an infrequent cause of community-acquired adult pneumonia,1 it is common among children2 and may become life threatening in immunocompromised patients, such as hematopoietic stem cell recipients.3-5 Among these high-risk persons, PIV type 3 (PIV-3) is the most prevalent serotype.6,7 Here, we report the case of a patient with pre-T-cell lymphoma who developed lower respiratory tract infection with this virus and was successfully treated with interferon alfa-2b.
The patient was a 41-year-old man with a history of a pre-T-cell non-Hodgkin lymphoma showing features of acute lymphoblastic leukemia. He was admitted with increasing dyspnea and cough during the previous week (Fig. 1). One day before presentation, he had experienced a fever of 101.4°F, with chills and mild hemoptysis. Earlier that day, he had undergone a bronchoscopy as part of an evaluation of a 1.6-cm left lower lobe nodule found during a pre-bone marrow transplant evaluation.
The patient was originally diagnosed as having lymphoma in July of 2004 and received chemotherapy and radiation therapy at that time. His therapy was complicated by sepsis with Stomatococcus species and Abiotrophia species bacteremia. He was on replacement-dose steroids for adrenal insufficiency and at the time of presentation had been on moxifloxacin and voriconazole for 9 days. On physical examination, his temperature was 100.8°F, and his breath sounds were decreased bilaterally, with crackles in both lower lobes. He was in no respiratory distress, and the remainder of his physical examination was unremarkable.
His white blood cell was 4390 cells/mm3, creatinine level was 1.2 mg/dL, and liver function tests were within reference ranges. Blood, sputum, and urine cultures were also negative. The bronchoalveolar lavage taken the day before admission grew 1 colony of Aspergillus fumigatus, and a respiratory viral panel was positive for human PIV-3. New bilateral ground-glass infiltrates and a stable left lower lobe pulmonary nodule appeared on computerized tomography (CT) scan. The patient was treated with micafungin and voriconazole for his presumed fungal nodular pneumonia, and steroids were administered for the viral infection. After his fever resolved and his respiratory symptoms improved, he was discharged on a 7-day tapering course of steroids and micafungin-voriconazole.
Eleven days later, the patient was readmitted with recurrence of fevers of 103°F and worsening dry cough. Blood, urine, and bacterial cultures were again negative. A repeat CT scan of the chest showed worsening ground-glass infiltrates and a new consolidation in the left lower lobe (Fig. 2). He had also become hypoxic, with coarse bilateral breath sounds. The patient was restarted on broad-spectrum antibiotics and increased doses of steroids. Pneumocystis jirovecii pneumonia was ruled out by negative cytology studies. A throat swab for a respiratory viral panel was again positive for PIV-3, and the patient was started on inhaled rivabirin and intravenous immunoglobulin (IVIG) without any improvement. A repeat CT scan of the chest on day 21 of admission showed worsening infiltrates, and the patient was then started on interferon alfa-2b, 10 million units subcutaneously 3 times a week. The bronchoalveolar lavage confirmed human PIV-3 and came back positive for cytomegalovirus (CMV). A polymerase chain reaction of whole blood for CMV was negative. Nonetheless, the patient was started on intravenous gancyclovir and anti-CMV immunoglobulin.
Four days after initiating interferon alfa-2b therapy, the patient began to show signs of improvement with decreased oxygen requirements and decreased dyspnea. His respiratory viral panel reverted to negative for human PIV-3, and a CT scan of the chest on day 28 of admission revealed improved aeration and diminished pulmonary infiltrates (Fig. 3). On day 31, he was discharged to complete 2 further weeks of interferon alfa-2b therapy, 4 more days of valgancyclovir, and 3 months of voriconazole.
On a follow-up visit 3 weeks after discharge, he had stopped using supplemental oxygen and was free of respiratory symptoms. The CT scan of the chest showed significant improvement.
There is as yet no adequate treatment of human PIV infection in the immunocompromised patient. Although there have been some case reports of positive outcomes with rivabirin and IVIG,8,9 others have failed to show any benefit.6 Interferon alfa has been shown to significantly decrease human PIV-3 replication in experimental models,10 inhibiting viral multiplication via several pathways.11 Despite rivabirin and IVIG therapy, our patient showed continued clinical deterioration, increased oxygen requirements, and a deteriorating radiological picture. Given the animal model data, we opted for a trial of interferon alfa-2b therapy. A marked response was evident during the first week. There was decreased oxygen requirement, improvement on imaging studies, and later, clearance of human PIV from nasopharyngeal secretions.
Cytomegalovirus and A. fumigatus were detected in bronchoalveolar lavage samples from our patient. In a large retrospective study of hematopoietic stem cell transplant recipients infected with human PIV, these 2 agents caused the majority of coinfections and produced a much greater mortality than did those without coinfection.6
It is difficult to assess the relative contributions of these 2 pathogens to the clinical deterioration observed during the first 3 weeks of our patient's second hospital admission. He was already on adequate antifungal therapy at the time of presentation, and although anti-CMV therapy was started only 2 days after the interferon alfa-2b, the diagnostic evidence for CMV pneumonia in this case was not substantial. One sample of respiratory secretions was positive for CMV, and the polymerase chain reaction from blood was negative. Notably, only after the start of interferon alfa-2b and subsequent clinical improvement did the throat swab for PIV-3 became negative.
Human PIV-3 infection can be a devastating disease in immunocompromised individuals, and more effective antiviral therapies are clearly needed. Our case study suggests that interferon alfa-2b may be a promising option. Prospective studies to confirm our findings would be worthwhile.
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