scholarly journals Human Rhinovirus Infections in Hematopoietic Cell Transplant Recipients: Risk Score for Progression to Lower Respiratory Tract Infection

2019 ◽  
Vol 25 (5) ◽  
pp. 1011-1021 ◽  
Author(s):  
Alpana Waghmare ◽  
Hu Xie ◽  
Jane Kuypers ◽  
Mohamed L. Sorror ◽  
Keith R. Jerome ◽  
...  
Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3229-3229
Author(s):  
Fiona L. Dignan ◽  
Caroline L. Alvares ◽  
Unell Riley ◽  
Mark E. Ethell ◽  
David C. Cunningham ◽  
...  

Abstract Parainfluenza virus type 3 (PIV 3) is a well recognised cause of respiratory illness after stem cell transplant (SCT) with an estimated incidence of 2–7%.(Wendt et al. N Engl J Med1992; 326: 921–926, Nichols et al. Blood2001; 98: 573–578). Persistently high mortality rates have been documented in this population. The largest series to date reported 75% mortality from PIV 3 lower respiratory tract infection.(Nichols et al). Treatment options are limited. There are anecdotal reports of successful use of ribavirin treatment but no randomised controlled trials have been undertaken.We undertook a retrospective review of 23 cases of PIV 3 occurring in adult SCT recipients over a 12 month period. A total of 145 patients had received a SCT in the same time period and 20 developed PIV3 infection (13.8%). The frequency of infection was 36.1% (13 of 36) in matched unrelated donor SCT recipients, 23.8% (5 of 21) in sibling allogenic SCT recipients and only 2.3% (2of 88) in autologous transplant recipients. Fourteen patients had received Campath 1-H as part of their conditioning regimen. The remaining three PIV 3 cases had a transplant date prior to the 12 month period. The median time from transplant to PIV 3 diagnosis was 54 days (range −7 to 2037 days). Only 6 cases were inpatients at diagnosis. Seventeen cases were outpatient or community acquired despite standard infection control procedures. Cases were identified by nasopharyngeal aspirate taken at the first sign of coryzal symptoms. Immunofluorescence (IF) identified PIV 3 in 13 patients and the virus was cultured in the remaining 10 cases. Eleven patients developed only upper respiratory tract symptoms and all survived. Lower respiratory tract symptoms and signs developed in 12 patients, of which 8 had a new infiltrate on chest X-ray. Four patients required invasive ventilation and one required non-invasive ventilation. Overall mortality at 30 days from PIV3 diagnosis was 4% (1 of 23). Three patients died in total but PIV 3 was not believed to be the primary cause of death in any of these patients. Autopsy confirmed post transplant lymphoproliferative disorder in one patient. The second case had septicaemia from a multiresistant coliform. Bronchoscopy in the remaining patient revealed invasive aspergillosis but IF and culture were negative for PIV 3. Early ribavirin treatment was administered in 8 patients. The primary indication for ribavirin treatment was lower respiratory tract infection. Six cases received aerosolised treatment, one intravenous and one patient received both aerosolised and IV therapy. Only one patient who received ribavirin treatment died. These results suggest a higher prevalence of PIV 3 but lower mortality than previously documented particularly in allogenic transplant recipients. We propose that the high prevalence reflects our unit policy of active surveillance for respiratory viruses and the difficulty in preventing transmission of PIV 3 especially in the outpatient setting. Ribavirin treatment may improve outcome in patients with lower respiratory tract infection but is not required in all patients with PIV 3 infection.


2021 ◽  
Vol 5 (7) ◽  
pp. 1903-1914
Author(s):  
Chikara Ogimi ◽  
Hu Xie ◽  
Alpana Waghmare ◽  
Masumi Ueda Oshima ◽  
Kanwaldeep K. Mallhi ◽  
...  

Abstract Data are limited regarding risk factors for lower respiratory tract infection (LRTI) caused by seasonal human coronaviruses (HCoVs) and the significance of virologic documentation by bronchoalveolar lavage (BAL) on outcomes in hematopoietic cell transplant (HCT) recipients. We retrospectively analyzed patients undergoing allogeneic HCT (4/2008-9/2018) with HCoV (OC43/NL63/HKU1/229E) detected by polymerase chain reaction during conditioning or post-HCT. Risk factors for all manifestations of LRTI and progression to LRTI among those presenting with HCoV upper respiratory tract infection (URTI) were analyzed by logistic regression and Cox proportional hazard models, respectively. Mortality rates following HCoV LRTI were compared according to virologic documentation by BAL. A total of 297 patients (61 children and 236 adults) developed HCoV infection as follows: 254 had URTI alone, 18 presented with LRTI, and 25 progressed from URTI to LRTI (median, 16 days; range, 2-62 days). Multivariable logistic regression analyses showed that male sex, higher immunodeficiency scoring index, albumin <3 g/dL, glucose >150 mg/dL, and presence of respiratory copathogens were associated with occurrence of LRTI. Hyperglycemia with steroid use was associated with progression to LRTI (P < .01) in Cox models. LRTI with HCoV detected in BAL was associated with higher mortality than LRTI without documented detection in BAL (P < .01). In conclusion, we identified factors associated with HCoV LRTI, some of which are less commonly appreciated to be risk factors for LRTI with other respiratory viruses in HCT recipients. The association of hyperglycemia with LRTI might provide an intervention opportunity to reduce the risk of LRTI.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S645-S645
Author(s):  
Chikara Ogimi ◽  
Emily T Martin ◽  
Hu Xie ◽  
Angela P Campbell ◽  
Alpana Waghmare ◽  
...  

Abstract Background Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. We examined incidence and disease spectrum of BoV respiratory tract infection (RTI) in HCT recipients. Methods In a longitudinal surveillance study of viral RTIs among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1-year post-HCT. Samples were tested by multiplex semi-quantitative PCR for RSV, parainfluenza virus 1–4, influenza A/B, adenovirus, human metapneumovirus, rhinovirus, coronavirus, and BoV. Plasma samples from BoV+ subjects were analyzed by PCR. In addition, we conducted a retrospective review of HCT recipients with BoV detected in bronchoalveolar lavage or lung biopsy. Results Among 469 patients in the prospective cohort, 21 distinct BoV RTIs (3 pre-HCT and 18 post-HCT) were observed by 1-year post-HCT in 19 patients (median 42 years old, range 0–67) without apparent seasonality. BoV was more frequently detected in the latter half of the first 100 days post-HCT (Figure 1). The frequencies of respiratory symptoms in patients with BoV detected did not appear to be higher than those without any virus detected, with the exception of watery eyes (P < 0.01) (Figure 2). Univariable models among patients with BoV RTI post-HCT showed higher peak viral load in nasal samples (P = 0.04) and presence of respiratory copathogens (P = 0.03) were associated with presence of respiratory symptoms; however, BoV detection in plasma was not (P = 0.8). Retrospective review identified 6 allogeneic HCT recipients (range 1–64 years old) with BoV detected in lower respiratory tract specimens [incidence rate of 0.4% (9/2,385) per sample tested]. Although all 6 cases presented with hypoxemia, 4 had significant respiratory copathogens or concomitant conditions that contributed to respiratory compromise. No death was attributed mainly to BoV lower RTI. Conclusion BoV is infrequently detected in respiratory tract in HCT recipients. Our studies did not demonstrate convincing evidence that BoV is a significant pathogen in either upper or lower respiratory tracts. Watery eyes were associated with BoV detection. Disclosures All authors: No reported disclosures.


Author(s):  
Chikara Ogimi ◽  
Emily T Martin ◽  
Hu Xie ◽  
Angela P Campbell ◽  
Alpana Waghmare ◽  
...  

Abstract Background Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. Methods In a longitudinal surveillance study among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then at least every 3 months through 1 year post-HCT at the Fred Hutchinson Cancer Research Center (2005–2010). Samples were tested by multiplex semiquantitative polymerase chain reaction (PCR) for 12 viruses. Plasma samples from BoV + subjects were analyzed by PCR. Separately, we conducted a retrospective review of HCT recipients with BoV detected in lower respiratory tract specimens. Results Among 51 children and 420 adults in the prospective cohort, 21 distinct BoV respiratory tract infections (RTIs) were observed by 1 year post-HCT in 19 patients. Younger age and exposure to children were risk factors for BoV acquisition. Univariable models among patients with BoV RTI showed higher peak viral load in nasal samples (P = .04) and presence of respiratory copathogens (P = .03) were associated with presence of respiratory symptoms, but BoV plasma detection was not. Only watery eyes and rhinorrhea were associated with BoV RTI in adjusted models. With additional chart review, we identified 6 HCT recipients with BoV detected in lower respiratory tract specimens (incidence rate of 0.4% [9/2509] per sample tested). Although all cases presented with hypoxemia, 4 had respiratory copathogens or concomitant conditions that contributed to respiratory compromise. Conclusions BoV RTI is infrequent in transplant recipients and associated with mild symptoms. Our studies did not demonstrate convincing evidence that BoV is a serious respiratory pathogen.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S918-S918
Author(s):  
Emily Ruth Levy ◽  
Theresa Madigan ◽  
Matthew Binnicker ◽  
jimmy mond ◽  
W Charles Huskins

Abstract Background Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infection (LRTI) in immunocompromised children. There is no standard effective treatment, though ribavirin (inhaled or oral), pooled human intravenous immunoglobulin (IVIG), and monoclonal anti-RSV antibody (palivizumab) have been described. RI-002 (ADMA Biologics Inc.) is a pooled human polyclonal IVIG that contains standardized levels of neutralizing anti-RSV antibodies. It was recently FDA-approved for prophylaxis in primary immunodeficiency patients and has been used as compassionate treatment for RSV LRTI in stem cell transplant patients. Methods Two children with T-cell lymphoblastic lymphoma, both undergoing delayed intensification chemotherapy, were diagnosed with RSV LRTI. They were both treated with RI-002 under an emergency FDA Investigational New Drug protocol. Results Patient 1, a 4-year-old boy, was admitted with fever, neutropenia and nasal congestion, and diagnosed with RSV infection on hospital day (HD) 5. On HD17, he was intubated for respiratory failure. IVIG, palivizumab, and daily oral ribavirin were administered. On HD18, he required high frequency oscillator ventilation, nitric oxide, and paralysis. He was given RI-002 (1.5 g/kg on HD20 and 0.75 g/kg on HD22). He was placed on veno-venous extracorporeal membrane oxygenation (ECMO) on HD23. RSV PCR crossing point (Cp) values trended higher, but remained positive (table). On HD33, RI-002 was re-dosed (0.75 g/kg). Pulmonary compliance and chest CTs improved (figure). On HD52, ECMO support was discontinued. He was discharged on HD88, and currently requires no respiratory support. Patient 2, a 5-year-old boy, was admitted with fever, neutropenia, nasal congestion, cough, and stridor and diagnosed with RSV infection (HD1). He required nasal cannula oxygen. IVIG and daily oral ribavirin were administered. He was given RI-002 (1.5 g/kg on HD3 and 0.75 g/kg on HD5). By HD5, he was afebrile; oxygen was discontinued. He was discharged HD6. Conclusion Human polyclonal IVIG containing standardized levels of neutralizing anti-RSV antibodies may be useful in the treatment of RSV LRTI in immunocompromised children. Future studies on the role of RI-002 in treatment of RSV infection in immunocompromised children are warranted. Disclosures All authors: No reported disclosures.


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