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Table 1. Incidence rates of respiratory syncytial virus infections and lower respiratory tract infections among symptomatic hematopoietic cell transplant recipients.
RSV in HCT and hematologic malignancies
30% to 37% of respiratory viral infections in this popula- tion, with approximately 19% to 36% of these infections resulting in LRTI.4,20 Determination of the true incidence of RSV infection among HCT recipients has been challeng- ing, with a reported wide range of 5% to 49%,5,8,18,21-28 as many studies included symptomatic patients diagnosed with different laboratory assays such as RSV antigen detection, identification of RSV by direct florescent anti- body, viral cultures, and molecular assays in recent years (Table 1). In addition, the wide range of reported inci- dences of RSV infections could be due to the increased awareness of this virus over the years and its impact on immunocompromised patients. On the other hand, lower incidences of RSV infections were reported in studies in which molecular assays such as multiplex polymerase chain reaction were used to detect RSV, with the reported range in these cases being 8-30%.8,9,29 This lower incidence could be explained by the increased rate of diagnosing other respiratory viruses, such as coronavirus, rhinovirus, and parainfluenza, with the use of molecular assays.
The proportion of RSV infections causing LRTI in HCT recipients ranges from 30% to 60% with higher rates reported in earlier years (in the early 1990s),5,21,22 whereas in more recent studies, since year 2000, lower rates of LRTI (24-44%) have been observed.4,11,23-25,29,30 This could possibly be explained by the increased use of ribavirin at earlier stages of RSV infection to prevent the infection from pro- gressing to the lower respiratory tract, as well as the use
of molecular assays for the detection not only of RSV but also other respiratory viruses. Recent studies from the Fred Hutchinson Cancer Research Center on respiratory viral infections in HCT patients applied specific defini- tions to better delineate the types of LRTI associated with respiratory viral infections.31 Patients with proven or prob- able LRTI were defined as patients with microbiological detection of respiratory viruses in the lower respiratory tract with or without radiological evidence of disease in the lungs, respectively. Patients with possible LRTI were defined as patients with microbiological detection of res- piratory viruses in the upper respiratory tract only and with radiological evidence of disease in the lungs.31 In one of the studies, the proportions of patients with proven/probable or possible RSV LRTI were 48% and 52%, respectively.31 Interestingly, the authors showed that patients with proven or probable LRTI had a higher need for supplemental oxygen use and for mechanical ventila- tion compared to those with possible LRTI. These defini- tions were also applied in studies on coronavirus,32 parain- fluenza virus33 and rhinovirus.34
Data on RSV infections in HM patients are scarce. Some studies have reported the rate of RSV infections in these patients.4,28,29,35-37 In an early study, the incidence of RSV was 31% among all symptomatic HM patients, including HCT recipients. A large proportion of these infections were diagnosed as LRTI (36%).29 Similar studies reported a range of 3% to 37%, but the sample sizes were relative-
Date of publication
1991
1996
2001
2002
2002
2003
2003
2003
2005
2009
2013
2014
Country
USA
USA
Multiple European nations
England
USA
Brazil
USA
England
Spain
Sweden
Brazil
Italy
Study type
Retrospective observational
Retrospective
observational
Prospective observational
Retrospective
observational
Retrospective observational
Prospective
observational
Prospective observational
Retrospective
observational
Prospective observational
Retrospective
observational
Retrospective observational
Prospective
observational
Detection methods
RSV antigen and viral culture
RSV antigen, viral culture
and pathology
RSV antigen and viral culture
RSV antigen and
viral culture
RSV DFA, RSV antigen and viral culture
RSV antigen
Viral culture and RSV PCR
RSV antigen
and viral culture
RSV antigen and viral culture
RSV antigen
and viral culture RSV PCR
RSV PCR
Percentage
of allogeneic HCT
73%
52%
90%
100%
89%
72%
45%
83%
54%
100%
29%
95%
Total number of RSV cases (%)
3 (5%)
33 (49%)
20 (10%)
13 (37%)
48 (9%)
27 (40%)
11 (30%)
6 (21%)
19 (11%)
32 (12%)
14 (14%)
21 (8%)
Percentage of LRTI
33%
61%
60%
46%
52%
56%
36%
33%
37%
44%
NA
11%
Authors
Garcia et al.18 Whimbey et al.21 Ljungman et al.5
Chakrabarti et al.23 Small et al.22 Machado et al.27 Roghmann et al.29 Hassan et al.26 Martino et al.28 Avetisyan et al.24 Moreira et al.8
Mikulska et al.7
HCT: hematopoietic cell transplant; RSV: respiratory syncytial virus; LRTI: lower respiratory tract infection; DFA: direct fluorescent antibody detection; PCR: polymerase chain reaction, NA: not available.
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