scholarly journals Predictive Value of Respiratory Viral Detection in the Upper Respiratory Tract for Infection of the Lower Respiratory Tract With Hematopoietic Stem Cell Transplantation

2019 ◽  
Author(s):  
Jim Boonyaratanakornkit ◽  
Meghana Vivek ◽  
Hu Xie ◽  
Steven A Pergam ◽  
Guang-Shing Cheng ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Upper Respiratory Tract ◽  
Hematopoietic Cell Transplant ◽  
Hematopoietic Stem ◽  
Logistic Regression Models ◽  
Upper Respiratory ◽  
Syncytial Virus

Abstract Background Hematopoietic cell transplant (HCT) recipients are frequently infected with respiratory viruses (RVs) in the upper respiratory tract (URT), but the concordance between URT and lower respiratory tract (LRT) RV detection is not well characterized. Methods Hematopoietic cell transplant candidates and recipients with respiratory symptoms and LRT and URT RV testing via multiplex PCR from 2009 to 2016 were included. Logistic regression models were used to analyze risk factors for LRT RV detection. Results Two-hundred thirty-five HCT candidates or recipients had URT and LRT RV testing within 3 days. Among 115 subjects (49%) positive for a RV, 37% (42 of 115) had discordant sample pairs. Forty percent (17 of 42) of discordant pairs were positive in the LRT but negative in the URT. Discordance was common for adenovirus (100%), metapneumovirus (44%), rhinovirus (34%), and parainfluenza virus type 3 (28%); respiratory syncytial virus was highly concordant (92%). Likelihood of LRT detection was increased with URT detection (oods ratio [OR] = 73.7; 95% confidence interval [CI], 26.7–204) and in cytomegalovirus-positive recipients (OR = 3.70; 95% CI, 1.30–10.0). Conclusions High rates of discordance were observed for certain RVs. Bronchoalveolar lavage sampling may provide useful diagnostic information to guide management in symptomatic HCT candidates and recipients.

scholarly journals A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplant Recipients

2019 ◽  
Vol 71 (11) ◽  
pp. 2777-2786 ◽  
Author(s):  
Roy F Chemaly ◽  
Sanjeet S Dadwal ◽  
Anne Bergeron ◽  
Per Ljungman ◽  
Yae-Jean Kim ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Weighted Average ◽  
Cell Transplant ◽  
Upper Respiratory Tract ◽  
Hematopoietic Cell Transplant ◽  
Double Blind ◽  
Time Weighted Average ◽  
Upper Respiratory ◽  
Syncytial Virus

Abstract Background Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections. Methods Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. Results From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, −0.33 log10 copies/mL; 95% confidence interval [CI] −.64 to −.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22–1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo. Conclusions Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia. Clinical Trials Registration NCT02254408; EUDRA-CT#2014-002474-36.

scholarly journals Does Detection of Respiratory Viral Infection in Upper Respiratory Tract (URT) Predict Lower Respiratory Tract (LRT) Disease in Hematopoietic Cell Transplant (HCT) Patients?

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S9-S9
Author(s):  
Meghana Vivek ◽  
Hu Xie ◽  
Steven A Pergam ◽  
Marco Mielcarek ◽  
Joshua Hill ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Regression Models ◽  
Cell Transplant ◽  
Upper Respiratory Tract ◽  
Multivariable Model ◽  
Hematopoietic Cell Transplant ◽  
Solitary Nodule ◽  
Logistic Regression Models ◽  
Paired Samples ◽  
Upper Respiratory

Abstract Background HCT recipients are frequently infected with respiratory viruses (RVs) in the URT; however, diagnostic evaluation of the LRT by bronchoalveolar lavage (BAL) is less common. We sought to determine whether the detection of RVs in the URT is predictive of LRT detection and to identify factors that predict discordance between upper and lower RV detection. Methods HCT recipients with respiratory symptoms and LRT RV testing via multiplex PCR in BAL from July 2009 to October 2016 were included in the study. RV PCR results, including cycle threshold (CT) values, were compared with URT samples obtained within ±3 days. Logistic regression models were used to analyze risk factors for RV discordance between paired samples. Results Among 1,000 HCT recipients with BAL RV testing, 250 had URT testing within 3 days. In total, 75(30%) sample pairs were concordant for the same RV in both the URT and BAL (P/P); 132 (53%) were negative from both sites. Among 43 discordant pairs, 25 (10%) were only positive by URT but negative by BAL (P/N) and 18 (7%) were positive by BAL but negative by URT (N/P). In pairs with positive RV results in the URT or BAL, discordance was common for HMPV (44%), HRV (33%), and PIV-3 (28%); RSV was almost always concordant (92%) (Figure 1). In a multivariable model, the risk of discordance (P/N or N/P) was increased in the presence of a solitary nodule on radiography (OR 6.8; 95% CI 1.2–38.3) and with lymphocyte count >500/mm3 (OR 3.1; 95% CI 1.08–9.0). Among P/P pairs, the median difference between CT values between URT and BAL samples was 0 (range −12 to +13), with 33 and 29% of subjects having lower and higher CT values (>4, ~1 log10) in the BAL, respectively (Figure 2). Conclusion In symptomatic HCT recipients with RV PCR testing performed concurrently in the upper and lower tract, discordant results are relatively common, especially for HRV, HMPV, and PIV-3. The presence of a solitary nodule on imaging and the absence of lymphopenia are associated with discordant results, with BAL results more likely being negative in these situations. More than half of the P/P pairs had a >4 difference in CT values between URT and LRT samples. Taken together, these data suggest that RV testing in BAL can provide useful diagnostic information that may guide management in HCT recipients. Disclosure S. A. Pergam, MERCK: Consultant and Investigator, Consulting fee.

scholarly journals Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cheng Lei ◽  
Lisong Yang ◽  
Cheong Tat Lou ◽  
Fan Yang ◽  
Kin Ian SiTou ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Pediatric Patients ◽  
Respiratory Infections ◽  
Upper Respiratory Tract ◽  
Viral Etiology ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao. Methods A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality. Results Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup. Conclusions This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.

scholarly journals A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Lower Respiratory Tract

2019 ◽  
Vol 71 (11) ◽  
pp. 2787-2795 ◽  
Author(s):  
Francisco M Marty ◽  
Roy F Chemaly ◽  
Kathleen M Mullane ◽  
Dong-Gun Lee ◽  
Hans H Hirsch ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Weighted Average ◽  
Supplemental Oxygen ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Average Change ◽  
Time Weighted Average ◽  
Syncytial Virus

Abstract Background Presatovir significantly reduced nasal viral load, signs, and symptoms of respiratory syncytial virus (RSV) infection in a human challenge study. We evaluated presatovir in hematopoietic-cell transplant (HCT) recipients with RSV lower respiratory tract infection (LRTI). Methods Patients with confirmed RSV in upper and lower respiratory tract and new chest X-ray abnormalities were randomized (1:1), stratified by supplemental oxygen and ribavirin use, to receive oral presatovir 200 mg or placebo every 4 days for 5 doses. The primary endpoint was time-weighted average change in nasal RSV viral load through day 9. Secondary endpoints included supplemental oxygen-free days, incident respiratory failure requiring mechanical ventilation, and all-cause mortality. Results From January 31, 2015, to March 20, 2017, 60 patients from 17 centers were randomized (31 presatovir, 29 placebo); 59 received study treatment (50 allogeneic, 9 autologous HCT). In the efficacy population (29 presatovir, 28 placebo), presatovir treatment did not significantly reduce time-weighted average change in viral load (−1.12 vs −1.09 log10 copies/mL; treatment difference −0.02 log10 copies/mL, 95% confidence interval: −.62, .57; P = .94), median supplemental oxygen-free days (26 vs 28 days, P = .84), incident respiratory failure (10.3 vs 10.7%, P = .98), or all-cause mortality (0 vs 7.1%, P = .19) versus placebo. Adverse events were similar between arms (presatovir 80%, placebo 79%). Resistance-associated substitutions in RSV fusion protein emerged in 6/29 presatovir-treated patients. Conclusions Presatovir treatment was well tolerated in HCT patients with RSV LRTI but did not improve virologic or clinical outcomes versus placebo. Clinical Trials Registration www.clinicaltrials.gov, NCT02254421; EudraCT, #2014-002475-29

scholarly journals Role of Human Bocavirus Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients

2020 ◽  
Author(s):  
Chikara Ogimi ◽  
Emily T Martin ◽  
Hu Xie ◽  
Angela P Campbell ◽  
Alpana Waghmare ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Hematopoietic Cell ◽  
Respiratory Pathogen ◽  
Human Bocavirus ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Tract Infections ◽  
The Impact

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.

Epidemiology and Outcomes of Respiratory Virus Infections in Adult Acute Leukemia and Hematopoietic Stem Cell Transplant Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4984-4984
Author(s):  
Gaurav Trikha ◽  
Rebecca Conway ◽  
John W Hiemenz ◽  
Per T. Ljungman
Keyword(s):  
Respiratory Tract ◽  
Acute Leukemia ◽  
Multiplex Pcr ◽  
Respiratory Virus ◽  
Cell Transplant ◽  
Upper Respiratory Tract ◽  
Virus Infections ◽  
Hematopoietic Stem ◽  
Upper Respiratory ◽  
Respiratory Virus Infections

Abstract BACKGROUND Respiratory virus infections (RVI) are significant cause of morbidity and mortality in adult patients with hematopoietic stem cell transplant (HSCT) recipients, causing delay in administering chemotherapy and HSCT, increased hospital stay and in occasionally resulting in mortality. In 2008, the FDA approved the use of multiplex PCR assay to detect respiratory viruses. Our institution has been using the multiplex PCR technique for approximately four years. With this technology the time to diagnosis of a RVI became shorter and detection of multiple viruses at the same time became feasible. RVIs have been studied more exclusively in the HSCT population where lymphopenia has been identified for poor outcomes. These infections have been less well studied in the acute leukemia population. This report, however, encompasses both patient populations. The natural progression of RVIs apart from influenza is poorly understood. The viruses isolated from the upper respiratory tract, development of lower respiratory tract infection (LRI), as well as overall survival of the patients identified with RVIs are reported here. STUDY DESIGN This is a retrospective cohort study of adult patients (>=18yrs) with acute leukemia and/or after HSCT diagnosed with laboratory documented RVI between May 1st 2010 and March 1st2014. A list of positive RVIs from multiplex PCR was retrieved from the hospital laboratory based on patients with specific ICD-9 codes. RESULTS Between May 2010 to March 2014, there were 208 episodes of RVI in 122 patients. Out of these, 77 patients were post-HSCT and 45 patients had acute leukemia without undergoing HSCT. Out of these episodes, 85 were caused by rhinovirus, 37 by coronavirus, 18 by RSV, 35 by parainfluenza, 15 by influenza, 12 by metapneumovirus, 3 by adenovirus, 3 by poly-viral infection. 189 episodes were initially diagnosed as an upper respiratory tract infection (URI). There were 47 episodes of LRI; of these 32 (16.9%) had a prior URI with rhinovirus (n=13), coronavirus (n=5), parainfluenza (n=4), RSV (n=4), influenza (n=3) and poly-viral infections (n=2). 15 (7.2%) episodes were LRI at initial presentation (4 metapneumovirus, 4 parainfluenza, 2 RSV, 3 rhinovirus, 1 coronavirus, 1 adenovirus). Out of the 122 patients there were 7 deaths (5.7%). CONCLUSION The availability of multiplex PCR has allowed for the identification of respiratory viruses responsible for URI in this patient population. Most of these infections have limited clinical consequences. However, in our study 25% of the episodes either presented with or progressed to LRI. The exact role of respiratory virus in causing LRI is difficult to determine in a retrospective study. Disclosures Off Label Use: Treating MDS with one of these regimens: (1) nelfinavir, (2) bortezomib, (3) metformin + simvastatin, (4) metformin + seliciclib, (5) nelfinavir + bortezomib, (6) nelfinavir + ruxolitinib, (7) nelfinavir + simvastatin, (8) nelfinavir + sorafenib, (9) nelfinavir + trametinib, (10) ponatinib + bortezomib, (11) nelfinavir + ponatinib, and (12) trametinib + simvastatin.

scholarly journals Risk factors for seasonal human coronavirus lower respiratory tract infection after hematopoietic cell transplantation

2021 ◽  
Vol 5 (7) ◽  
pp. 1903-1914
Author(s):  
Chikara Ogimi ◽  
Hu Xie ◽  
Alpana Waghmare ◽  
Masumi Ueda Oshima ◽  
Kanwaldeep K. Mallhi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract Infection ◽  
Lower Respiratory Tract ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Upper Respiratory Tract

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.

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