Alpana Waghmare

Respiratory syncytial virus lower respiratory disease in hematopoietic cell transplant recipients: viral RNA detection in blood, antiviral treatment, and clinical outcomes

Respiratory syncytial virus (RSV) RNA detection in plasma or serum may be a marker for lung injury and poor outcomes in hematopoietic cell transplant recipients with RSV lower respiratory disease. Treatment with aerosolized ribavirin appeared protective against overall and pulmonary mortality.

Respiratory Syncytial Virus in Hematopoietic Cell Transplant Recipients: Factors Determining Progression to Lower Respiratory Tract Disease

Abstract Background. Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD. Methods. This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI. Results. In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm3 at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm3 at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression. Conclusions. Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted.

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

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. Conclusion 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.

How I treat respiratory viral infections in the setting of intensive chemotherapy or hematopoietic cell transplantation

The widespread use of multiplex molecular diagnostics has led to a significant increase in the detection of respiratory viruses in patients undergoing cytotoxic chemotherapy and hematopoietic cell transplantation (HCT). Respiratory viruses initially infect the upper respiratory tract and then progress to lower respiratory tract disease in a subset of patients. Lower respiratory tract disease can manifest itself as airflow obstruction or viral pneumonia, which can be fatal. Infection in HCT candidates may require delay of transplantation. The risk of progression differs between viruses and immunosuppressive regimens. Risk factors for progression and severity scores have been described, which may allow targeting treatment to high-risk patients. Ribavirin is the only antiviral treatment option for noninfluenza respiratory viruses; however, high-quality data demonstrating its efficacy and relative advantages of the aerosolized versus oral form are lacking. There are significant unmet needs, including data defining the virologic characteristics and clinical significance of human rhinoviruses, human coronaviruses, human metapneumovirus, and human bocavirus, as well as the need for new treatment and preventative options.

Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality

Human rhinoviruses are the most common respiratory viruses detected in patients after hematopoietic cell transplantation. Although rhinovirus appears to occasionally cause severe lower respiratory tract infection in immunocompromised patients, the clinical significance of rhinovirus detection in the lower respiratory tract remains unknown. We evaluated 697 recipients transplanted between 1993 and 2015 with rhinovirus in respiratory samples. As comparative cohorts, 273 recipients with lower respiratory tract infection caused by respiratory syncytial virus (N=117), parainfluenza virus (N=120), or influenza (N=36) were analyzed. Factors associated with mortality were analyzed using Cox proportional hazard models. Among 569 subjects with rhinovirus upper respiratory tract infection and 128 subjects with rhinovirus lower respiratory tract infection, probabilities of overall mortality at 90 days were 6% and 41%, respectively (P<0.001). The survival rate after lower respiratory tract infection was not affected by the presence of co-pathogens (55% in patients with co-pathogens, 64% in patients without, P=0.34). Low monocyte count (P=0.027), oxygen use (P=0.015), and steroid dose greater than 1 mg/kg/day (P=0.003) before diagnosis were significantly associated with mortality among patients with lower respiratory tract infection in multivariable analysis. Mortality after rhinovirus lower respiratory tract infection was similar to that after lower respiratory tract infection by respiratory syncytial virus, parainfluenza virus or influenza in an adjusted model. In summary, transplant recipients with rhinovirus detection in the lower respiratory tract had high mortality rates comparable to viral pneumonia associated with other well-established respiratory viruses. Our data suggest rhinovirus can contribute to severe pulmonary disease in immunocompromised hosts.

Severe Drug Hypersensitivity Reaction in a Young Woman Treated with Doxycycline

Doxycycline is a commonly prescribed medication for the management of acne vulgaris. Severe adverse reactions to this medication are uncommon. We describe an unusual case of a 20-year-old female who experienced a life-threatening hypersensitivity reaction, including fever, lymphadenopathy, hepatitis, nephritis and severe pneumonitis with respiratory failure following oral administration of doxycycline for facial acne.

Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution

Summary Prolonged shedding of human coronavirus in hematopoietic cell transplant recipients was associated with initial high viral load, high-dose steroids, and myeloablative conditioning regimens. No substantial intrahost evolution of viral genomes occurred over time.

Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies

Summary Coronavirus pneumonia is associated with high rates of oxygen use and mortality in hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancies; mortality in HCT recipients is similar to that seen with respiratory syncytial virus, influenza, and parainfluenza virus.

Respiratory syncytial virus in hematopoietic cell transplant recipients

Abstract Background. Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD. Methods. This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI. Results. In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm3 at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm3 at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression. Conclusions. Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted.

Supplemental Oxygen–Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus

Confirmation of respiratory syncytial virus (RSV) in the lower respiratory tract is associated with worse clinical outcomes, including increased supplemental oxygen use, decreased supplemental oxygen–free days, and greater mortality rate. Supplemental oxygen–free days as a clinical end point may allow smaller sample sizes for trials evaluating RSV antivirals.