A Prospective Study Comparing Human Metapneumovirus with Other Respiratory Viruses in Adults with Hematologic Malignancies and Respiratory Tract Infections

Article (PDF Available)inThe Journal of Infectious Diseases 192(6):1061-5 · October 2005with21 Reads
DOI: 10.1086/432732 · Source: PubMed
Abstract
Human metapneumovirus (hMPV) is a recently described paramyxovirus associated with upper and lower respiratory-tract infection (URI and LRI, respectively). We conducted a prospective study of URI and LRI in adults with hematologic malignancies during a 4-year period. We retrospectively tested samples by reverse-transcription polymerase chain reaction for hMPV and analyzed clinical data. Twenty-two (9%) of 251 episodes of respiratory infection tested positive for hMPV. Sixteen (73%) of the illnesses occurred in hematopoietic stem-cell transplant recipients. Nine patients with hMPV developed LRI; 3 of these patients died. hMPV is a common cause of respiratory infections in adults with hematologic malignancies, with associated morbidity and mortality
BRIEF REPORT JID 2005:192 (15 September) 1061
BRIEF REPORT
A Prospective Study Comparing
Human Metapneumovirus with Other
Respiratory Viruses in Adults
with Hematologic Malignancies
and Respiratory Tract Infections
John V. Williams,
1
Rodrigo Martino,
3
Nu´ria Rabella,
4
Magdalena Otegui,
4
Rocio Parody,
3
Joshua M. Heck,
1
and James E. Crowe, Jr.
1,2
Departments of
1
Pediatrics and
2
Microbiology and Immunology, Vanderbilt
University Medical Center, Nashville, Tennessee;
3
Division of Clinical
Hematology and
4
Department of Microbiology, Hospital de la Santa Creu
i Sant Pau, Barcelona, Spain
Human metapneumovirus (hMPV) is a recently described
paramyxovirus associated with upper and lower respiratory-
tract infection (URI and LRI, respectively). We conducted a
prospective study of URI and LRI in adults with hematolog-
ic malignancies during a 4-year period. We retrospectively
tested samples by reverse-transcription polymerase chain re-
action for hMPV and analyzed clinical data. Twenty-two (9%)
of 251 episodes of respiratory infection tested positive for
hMPV. Sixteen (73%) of the illnesses occurred in hematopoi-
etic stem-cell transplant recipients. Nine patients with hMPV
developed LRI; 3 of these patients died. hMPV is a common
cause of respiratory infections in adults with hematologic ma-
lignancies, with associated morbidity and mortality.
Respiratory viruses—including respiratory syncytial virus (RSV),
influenza virus, and parainfluenza virus (PIV)—have been as-
sociated with severe pneumonia in patients receiving chemo-
therapy, especially in hematopoietic stem-cell transplant (HSCT)
recipients [1–8]. Human metapneumovirus (hMPV) is a recent-
ly described paramyxovirus that has been associated with acute
upper and lower respiratory-tract infection (URI and LRI, re-
Received 26 January 2005; accepted 18 April 2005; electronically published 12 August
2005.
Potential conflicts of interest: none reported.
Financial support: Fondo de Investigaciones Sanitarias (grant FIS 00/0296 toR.M.); National
Institutes of Health (grant R03-AI54760 to J.V.W.).
Reprints or correspondence: Dr. John V. Williams, Dept. of Pediatrics, Div. of Pediatric
Infectious Diseases, Vanderbilt University Medical Center, D-7235 MedicalCenter North, 1161
21st Ave. South, Nashville, TN 37232-2581 (john.williams@vanderbilt.edu).
The Journal of Infectious Diseases 2005;192:1061–5
2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19206-0017$15.00
spectively) in children and adults [9–13]. There have been 2
reports of fatal hMPV infection in patients with leukemia [14,
15]. We retrospectively tested samples from a previous prospec-
tive study of respiratory virus infections in adults with hema-
tologic malignancies [5], to determine the epidemiological and
clinical features of hMPV infection in these patients.
Patients and methods. The present prospective study was
conducted at the Division of Clinical Hematology, Hospital de
la Santa Creu i Sant Pau (Barcelona, Spain), from 1 October
1999 through 31 July 2004. All inpatient or outpatient adults
with a hematologic malignancy (including HSCT recipients)
who had signs and symptoms of URI or LRI underwent a
detailed clinical evaluation. Patients with symptoms of URI
underwent nasopharyngeal aspiration (NPA), whereas patients
with LRI underwent bronchoalveolar lavage (BAL) when it was
clinically possible. Patients with pneumonia but no signs of
URI did not undergo NPA. The study was approved by the
institutional review board of both author-affiliated institutions.
URI was defined as new onset of nasal, pharyngeal, or laryn-
geal irritation. LRI was defined as cough, rales, and/or wheezing
in conjunction with a new pulmonary infiltrate identified on
a chest radiograph. Progression of URI to LRI was defined as
the development of pneumonia in patients with prior or con-
current URI. Patients with a diagnosis of pneumonia in the
absence of URI were considered to have an isolated LRI. Re-
spiratory virus infections were considered to be nosocomial if
the onset of illness occurred after the patient had been hos-
pitalized for 3 days. We defined death from pneumonia as
that which occurred when a patient died of respiratory failure
during the episode of LRI.
All clinical samples were kept on ice and were processed
within 2 h. All samples were tested for viral antigen by direct
immunofluorescence assays for RSV; PIV-1, -2 or -3; influen-
za A or B; and adenoviruses. Samples were cultured for viruses
and tested by reverse-transcription polymerase chain reaction
(RT-PCR) for enterovirus as described elsewhere [5]. BAL sam-
ples were processed for bacterial, mycobacterial, and fungal
culture and for parasite examination. Aliquots from BAL and
NPA samples were stored at 70C.
NPA and BAL samples were thawed at 37C, and RNA was
extracted by use of the RNeasy kit (Qiagen). RT-PCR was per-
formed in duplicate by use of the OneStep RT-PCR kit (Qia-
gen). Primers amplified a 170-bp fragment of the L (polymer-
ase) gene that is highly conserved among hMPV isolates [9,
13]. Samples were considered to be positive if they were positive
in 2 reactions.
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1062 JID 2005:192 (15 September) BRIEF REPORT
Samples were also inoculated onto monolayers of LLC-MK2
cells in OptiMEM medium (Invitrogen) with trypsin and were
assessed 3 times weekly. Wells showing cytopathic effects were
tested for the presence of hMPV by RT-PCR. Cultures without
cytopathic effect were passaged onto fresh cells after 14 days
and then incubated for an additional 14 days.
Comparisons of patient- and disease-related variables be-
tween virus groups were performed by use of Fisher’s exact
test. Univariate analyses of the risk factors for progression to
LRI were performed by use of Fisher’s exact test for discon-
tinuous variables and by Student’s ttest or the Mann-Whitney
Utest for continuous variables. Multivariate analysis of vari-
ables predictive of development of an LRI was performed by
use of Cox proportional-hazards regression, with the inclusion
of variables with in the prior univariate testing. Age and
P!.1
neutrophil and lymphocyte counts were included as continu-
ous variables and as binary variables (more than or less than
a fixed value). The other factors that were analyzed were age,
sex, disease group (leukemia/myelodysplasia vs. lymphoid ma-
lignancies), disease status (nonadvanced vs. advanced), HSCT
(none vs. autologous HSCT vs. allogeneic HSCT), the presence
of severe lymphopenia (!cells/L) or neutropenia
9
0.2 10
(!0.510
9
cells/L) at the time of virus infection, the devel-
opment of acute or chronic graft-versus-host disease (GVHD;
only for allogeneic HSCT recipients, analyzed as a time-de-
pendent covariable), nosocomial infection, recent use of high-
dose corticosteroids (defined as 1 mg/kg of prednisone daily
or an equivalent for 11 week), and virus isolated (hMPV vs.
other/none). Tests of significance were 2 sided, and was
P!.05
considered to be statistically significant.
Results. During the 4-year study period, there were 304
separate episodes of respiratory infection that occurred in 128
patients. Results for viruses other than hMPV for patients re-
cruited between October 1999 and May 2001 have been re-
ported elsewhere [5]. The overall male:female ratio was 1.5:1,
and the mean age was 49 years (range, 20–72 years). The dis-
tribution of underlying diseases is listed in table 1.
Overall, 156 (51%) of 304 of the samples tested positive for
a respiratory virus. The number of samples with each virus and
sample type is shown in table 1. During the study period, we
monitored a total of 494 HSCT recipients (198 allogeneic and
296 autologous) at the medical center. Thus, 112 (23%) of 494
of HSCT recipients had a respiratory virus infection. Two hun-
dred fifty-one samples had remaining aliquots available for
hMPV testing. hMPV was detected in 22 (9%) of 251 samples
from 22 patients. hMPV was detected in 16 (8%) of 207 NPA
samples and in 6 (14%) of 44 BAL samples. The most frequent-
ly detected virus was influenza virus, which was found in 68
(22%) of 304 samples from patients with respiratoryinfections,
whereas RSV was detected in 27 (9%) of 304 samples from
patients with respiratory infections. There was a community-
wide influenza outbreak in 2000 that accounted for 20 of the
influenza infections. Fifty-two (17%) of the episodes were coin-
fections with 11 virus.
Table 1 lists the characteristics of the patients who were
infected with hMPV and other viruses. The mean age of patients
infected with hMPV was 50 years (range, 23–62 years), which
did not differ significantly from that of patients infected with
other viruses, and one-half of these patients weremale. Seventy-
seven percent of the hMPV infections occurred during winter
(36%) and spring (41%) months, in contrast to influenza and
RSV, which both were most prominent (77% and 78%, re-
spectively) during winter months. There was no year-to-year
variability in the number of hMPV infections detected. The
infection was considered to be community acquired in 55%
and nosocomially acquired in 45% of infections, similar to the
proportion of community-acquired versus nosocomial infec-
tions for the other viruses (P, not significant). Sixteen (73%)
of 22 of the hMPV-infected patients were HSCT recipients, who
were a mean of 144 days posttransplant (range, 1–488 days),
which was not different from the time of onset of all respira-
tory infections in HSCT recipients (mean, 169 days; range, 3–
963 days). There was a trend toward more-advanced under-
lying disease in the hMPV-infected patients, compared with
those infected with influenza virus ( ) but not compared
Pp.08
with those infected with other viruses (P, not significant).
The characteristics and outcomes of patients with hMPV and
other respiratory virus infections are shown in table 2. hMPV
was the primary virus isolated in 18 (82%) of 22 episodes of
respiratory infection, whereas, in 4 cases, hMPV infection was
detected after infection with another virus had been diagnosed;
it was thus considered to be a superinfection. This profile dif-
fered only from that of influenza virus, which was the primary
viral isolate in 66 (97%) of 68 of respiratory infections (Pp
). The majority of patients infected with hMPV presented
.03
with URI alone (20/22 [91%]); the rate did not differ signifi-
cantly from rates in patients infected with other viruses. One
patient presented with both URI and LRI, and 1 patient pre-
sented with only fever. Nine (41%) of the hMPV-infected pa-
tients were coinfected with 1 respiratory virus, as shown in
table 2. This frequency was similar to the frequency of coin-
fection seen with all other viruses except enterovirus (Pp.03).
Sixteen (73%) of 22 of hMPV-infected patients had lympho-
penia, whereas only 3 (14%) had neutropenia.
Eight of the hMPV-infected patients who presented with URI
alone subsequently progressed to LRI. Thus, 9 (41%) of 22 of
the hMPV-infected patients developed LRI. A similar propor-
tion of patients infected with other viruses except rhinovirus
presented with or progressed to LRI (P, not significant). Three
(33%) of hMPV-infected patients with LRI died, 2 of whom
had potential bacterial copathogens as determined by BAL
(Pseudomonas aeruginosa and Stenotrophomonas maltophilia).
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Table 1. Characteristics of patients in the present study of respiratory virus infections in adults with hematologic malignancies, by virus isolated.
Characteristic
Result in patients infected with
TotalhMPV Influenza virus RSV PIV1 or PIV3 Adenovirus Rhinovirus Enterovirus
No. of episodes positive for a virus/no. of episodes tested
a
22/251 (9) 68/304 (22) 27/304 (9) 15/304 (5) 12/304 (4) 3/304 (1) 9/304 (3) 146/304 (48)
b
Male 11 (50) 42 (62) 15 (55) 10 (67) 7 (58) 1 (34) 8 (89) 94 (60)
Age, median (range), years 50 (23–62) 51 (22–72) 48 (25–72) 48 (21–66) 45 (23–56) 37 (33–40) 45 (20–54) 49 (20–72)
Seasonal occurrence
Autumn 1 (5) 4 (6) 1 (4) 2 (13) 1 (8) 1 2 (22) 12 (8)
Winter 8 (36) 52 (77) 21 (78) 4 (27) 8 (67) 1 4 (45) 98 (62)
Spring 9 (41) 9 (13) 5 (18) 4 (27) 1 (8) 1 3 (33) 32 (21)
Summer 4 (18) 3 (4) 5 (33) 2 (17) 14 (9
Source of infection
Community acquired 12 (55) 50 (74) 17 (63) 10 (67) 10 (83) 1 7 (78) 107 (68)
Hospital acquired 10 (45) 18 (26) 10 (37) 5 (33) 2 (17) 2 2 (22) 49 (32)
Underlying disease
Acute leukemia/myelodysplastic syndrome 10 (45) 22 (32) 8 (30) 3 (20) 5 (42) 2 2 (22) 52 (33)
Chronic myeloid leukemia 2 (9) 11 (16) 2 (7) 2 (13) 1 (8) 18 (12)
Chronic lymphocytic leukemia 17 (25) 3 (11) 3 (20) 4 (33) 3 (33) 30 (19)
Non-Hodgkin lymphoma 2 (9) 3 (11) 2 (13) 1 (8) 2 (22) 10 (6)
Multiple myeloma 5 (23) 14 (20) 6 (22) 2 (13) 1 (8) 2 (22) 30 (19)
Hodgkin disease 3 (14) 2 (3) 5 (19) 2 (13) 1 13 (8)
Others 2 (3) 1 (7) 3 (2)
Type of treatment (interval between last chemotherapy and infection) 44 (29)
Chemotherapy (13 months) 2 13 4 2 2 23 (7)
Initial chemotherapy (!3 months) 4 5 2 … … 3 14 (11)
Salvage chemotherapy (!3 months) 2 4 6 (4)
HSCT type
Autologous 7 (32) 21 (31) 8 (30) 3 (20) 4 (33) 3 (33) 46 (31)
Allogeneic 9 (41) 26 (38) 13 (49) 6 (40) 6 (50) 3 3 (33) 66 (45)
Receipt of steroids 2 (9) 13 (19) 4 (15) 3 (20) 3 (24) 2 1 (11) 28 (19)
Status of underlying disease
c
Not advanced 10 (45) 40 (68) 16 (59) 8 (53) 8 (66) 1 7 (78) 90 (61)
Advanced 12 (55) 19 (32) 11 (41) 7 (47) 4 (34) 2 2 (22) 57 (39)
NOTE. Data are no. (%) of cases of infection, unless otherwise indicated. BAL, bronchoalveolar lavage; hMPV, human metapneumovirus; HSCT, hematopoietic stem-cell transplantation; LRI,lower respiratory-
tract infection; NPA, nasopharyngeal aspirate; PIV, parainfluenza virus; RSV, respiratory syncytial virus; URI, upper respiratory-tract infection.
a
No. of episodes sampled refers to all episodes of clinically defined URI and/or LRI that were included in a prospective study performed between 1 October 1999 and 31 July 2004, in which NPA and/or BAL
samples were tested. Several patients had 11 episode of viral infection during the study period; thus, the no. of distinct episodes (146) is higher than the no. of patients (128).
b
Nineteen patients had an episode of viral infection in which 2 viruses were identified; thus, the actual no. of episodes associated with viral infections was 146, rather than the apparent row total of 156.
c
Disease phase at transplant was categorized as not advanced (acute leukemia or poor-risk myelodysplasia in first complete remission, untreated good-risk myelodysplasia,first chronic-phase chronic myelogenous
leukemia, lymphoid malignancy in first remission, multiple myeloma in first complete or partial response after chemotherapy) or advanced (acute leukemia or myelodysplasia in second or highercomplete remission,
relapsed acute leukemia or myelodysplasia, accelerated and blastic-phase chronic myeloid leukemia, lymphoid malignancy in second or higher remission, refractory or relapsed lymphoid malignancy, orany indication
for a second transplant).
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1064 JID 2005:192 (15 September) BRIEF REPORT
Table 2. Characteristics of 156 respiratory virus infections, according to initial virus isolated.
Characteristic
Result in patients infected with
TotalhMPV
Influenza
virus RSV
PIV1
or PIV3 Adenovirus Rhinovirus Enterovirus
No. of infections 22 68 27 15 12 3 9 156
Nature of infection
Primary viral isolate
a
18 (82) 66 (97) 18 (67) 14 (93) 8 (67) 2 (67) 9 (100) 135 (87)
Superinfection
b
4 (18) 2 (3) 9 (33) 1 (7) 4 (33) 1 (33) 21 (13)
Clinical presentation
c
URI 20 (91) 54 (79) 20 (74) 11 (73) 10 (83) 3 (100) 7 (78) 125 (81)
LRI 8 (12) 1 (4) 2 (13) 1 (8) 1 (11) 13 (9)
URI + LRI 1 (5) 5 (7) 6 (22) 2 (13) 1 (8) 1 (11) 16 (10)
LRI (pneumonia) 9 (41) 20 (29) 11 (41) 6 (40) 5 (42) 0 2 (22) 53 (34)
Initial LRI URI 1 (5) 13 (65) 6 (22) 4 (27) 2 (17) 2 (22) 28 (18)
URI progressing to LRI 8 (36) 7 (35) 5 (18) 2 (13) 3 (25) 25 (16)
Neutropenia
d
3 (14) 8 (12) 4 (15) 3 (20) 4 (33) 1 (33) 23 (15)
Lymphopenia
e
16 (73) 27 (40) 14 (52) 6 (40) 6 (50) 2 (67) 3 (33) 74 (47)
Superinfection by another virus during episode
RSV 4
f
(18) 7 (10) 1 (8) 12 (8)
Adenovirus 1 (5) 3 (4) 1 (44) 1 (7) 6 (4)
CMV 1 (5) 1 (1) 1 (4) 1 (7) 4 (3)
Influenza A 2 (9) 3 (4) 12 (44) 1 (7) 5 (42) 1 (11) 24 (15)
PIV1 1 (8) 1 (33) 1 (11) 3 (2)
Enterovirus/rhinovirus 1 (5) 2 (14) 3 (2)
Respiratory-tract coinfections
Other respiratory virus 9 (41)
g
14 (20) 14 (52) 5 (33) 7 (58) 1 (33) 2 (22) 52 (33)
Bacterial 2 (9) 1 (1) 2 (8) 5 (3)
Aspergillus or other fungus 2 (3) 1 (7) 3 (2)
Death attributed to virus (% of LRI episodes) 3 (33) 4 (20) 3 (27) 2 (33) 2 (40) 0 0 12 (23)
No other copathogens found 1 0 1 2 2 5
Other copathogens involved 2 4 2 6
Invasive aspergillosis 1 1
Gram-negative bacilli 2 1 1 4
Cytomegalovirus … 2 1 3
NOTE. Data are no. (%) of cases of infection, unless otherwise indicated. CMV, cytomegalovirus; hMPV, human metapneumovirus; LRI, lower respiratory-
tract infection; PIV, parainfluenza virus; RSV, respiratory syncytial virus; URI, upper respiratory-tract infection.
a
Virus in the column was isolated at beginning of the respiratory illness.
b
Virus in the column was isolated later in the respiratory illness, after another virus had been isolated.
c
Two patients presented with fever alone; thus, URI, LRI, and URI + LRI cases total 154.
d
Neutrophil count, !cells/L.
9
0.510
e
Lymphocyte count, !cells/L.
9
0.210
f
One case of RSV infection was isolated 2 months after hMPV was detected.
g
Includes 1 sample that tested positive for CMV, herpes simplex virus, and hMPV.
One patient who died had no other viral, fungal, or bacterial
pathogens identified. Two of the patients who died were HSCT
recipients. All deaths occurred a median of 16 days (range, 3–
31 days) after the onset of LRI. Thus, the overall mortality in
the hMPV-infected patients was 14% (3/22), which did not
differ from that in patients infected with other viruses.
Twenty-nine (23%) of 125 patients who initially presented
with URI progressed to LRI, with a median interval between
URI and LRI of 9 days (range, 0–32 days). In univariate analysis,
risk factors for the progression of URI to LRI included (1)
having received an allogeneic HSCT (42% vs. 15%; ),P!.001
(2) having recently received high doses of steroids (40% vs.
20%; ), (3) the presence of lymphopenia (!
9
Pp.01 0.2 10
cells/L) at the onset of infection (60% vs. 18%; ), andP!.001
(4) having RSV (44% vs. 20%) or hMPV (41% vs. 19%) isolated
versus any other viruses—influenza A (20%), PIV 1–3 (27%),
adenovirus (25%), or picornaviruses (8%) ( for RSVPp.02
or hMPV vs. others). In multivariate analysis, risk factors were
(1) having received an allogeneic HSCT (hazard ratio [HR],
3.2 [95% confidence interval {CI}, 1.1–16.7]; ), (2) lym-Pp.05
phopenia (HR, 7.8 [95% CI, 2.5–23] ), and (3) infectionPp.02
with RSV or hMPV versus other viruses (HR, 4.0 [95% CI,
1.4–11]; ).Pp.01
Discussion. We conducted a prospective study of respira-
tory virus infections in adult patients with hematologic malig-
nancies, including HSCT recipients. We retrospectively tested
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BRIEF REPORT JID 2005:192 (15 September) 1065
samples from these patients and detected hMPV in 9% of acute
respiratory infections overall, similar to the frequency of RSV
in this cohort. This frequency is comparable to the frequencies
of influenza virus, RSV, and PIV infection previously docu-
mented in immunocompromised patients [1–5], which sug-
gests that hMPV is also a significant pathogen in this patient
population. The winter and spring prominence of hMPV in-
fections reflects the seasonal incidence of hMPV infections de-
scribed in previous studies [9–13]. A significant number of the
hMPV infections appeared to be nosocomial. In the majori-
ty of hMPV infections (18/22 [82%]), hMPV was the primary
virus isolated, which suggests that it alone was responsible for
the associated respiratory illness; overall, 9 (41%) of 22 hMPV-
infected patients were coinfected with other viruses.
Patients infected with hMPV had varying degrees of im-
munosuppression, which suggests that severe immune com-
promise is not a necessary risk factor for hMPV infection.
Similarly, the underlying disease status of hMPV-infected pa-
tients did not differ from that of patients infected with other
viruses, although there was a trend toward patients with hMPV
infection having a more advanced state of underlying disease,
compared with patients infected with influenza virus (Pp
). There was a high rate of lymphopenia (73%) in the.08
hMPV-infected patients, and 16 (73%) of 22 of these were
HSCT recipients. This observation may explain the higher rate
of progression of URI to pneumonia found in the multivariate
analysis in patients with URI caused by hMPV as opposed to
that caused by other viruses (except RSV).
Although the majority of hMPV-infected patients presented
with URI alone, 41% of these progressed to LRI; this is com-
parable to rates of patients with RSV and influenza progressing
to LRI in previous studies [1–4]. Of the 9 hMPV-infected pa-
tients with LRI, 3 (33%) died, and these deaths were attributable
to the LRI. One patient had no other viral, bacterial, or fungal
pathogens isolated from BAL samples, which suggests a primary
role for hMPV in the death. The other 2 patients had potential
bacterial pathogens isolated from BAL sample. Thus, at a min-
imum, 1 (5%) of 22 hMPV-infected patients—or 1 (11%) of
9 patients with LRIs caused by hMPV—died.
Exact comparisons between the prevalence of hMPV and
other viruses in this cohort are difficult to make, because hMPV
was detected by a sensitive molecular technique, whereas other
viruses (except enterovirus) were detected by a combination of
direct immunofluorescence, rapid antigen tests, and culture. A
further limitation of the study is the heterogeneity of under-
lying diagnoses and the degree of immune suppression. None-
theless, the prospective nature of sample and data collection in
the study and the recruitment of patients over a 4-year period
provide a unique framework to define the epidemiological and
clinical characteristics of hMPV infection in immunocom-
promised adults. Our data suggest that hMPV is a significant
respiratory pathogen in this population.
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by guest on May 14, 2011jid.oxfordjournals.orgDownloaded from
    • "Use of sensitive polymerase chain reaction (PCR) assay has led to increased awareness and identification of human metapneumovirus (hMPV) as a common cause of respiratory viral infection in hematopoietic cell transplant (HCT) recipients and hematologic malignancy (HM) patients. A recently discovered negative-sense RNA paramyxovirus, hMPV is genetically similar to respiratory syncytial virus (RSV) and it reportedly infects approximately 5%–9% of HCT recipients [1,2]. Progression of upper respiratory tract infection (URTI) to the lower respiratory tract infection (LRTI) occurs in 21%–40% of cases [3], with reported fatality rates of up to 80% in HCT recipients if bronchoalveolar lavage is positive for hMPV [4]. "
    [Show abstract] [Hide abstract] ABSTRACT: Over the past decade, reported incidence of human metapneumovirus (hMPV) has increased owing to the use of molecular assays for diagnosis of respiratory viral infections in cancer patients. The seasonality of these infections, differences in sampling strategies across institutions, and small sample size of published studies make it difficult to appreciate the true incidence and impact of hMPV infections. In this systematic review, we summarized the published data on hMPV infections in hematopoietic cell transplant recipients and patients with hematologic malignancy, focusing on incidence, hMPV-associated lower respiratory tract infection (LRTI), mortality, prevention, and management with ribavirin and/or intravenous immunoglobulins. Although the incidence of hMPV infections and hMPV-associated LRTI in this patient population is similar to respiratory syncytial virus or parainfluenza virus and despite lack of directed antiviral therapy, the mortality rate remains low unless patients develop LRTI. In the absence of vaccine to prevent hMPV, infection control measures are recommended to reduce its burden in cancer patients.
    Article · May 2016
    • "The CD8 + T cell (T CD8 ) response contributes to control of HMPV, as is the case for the related respiratory syncytial virus (RSV); in the absence of T CD8 , mice exhibit higher viral titers and delayed clearance [16,17] and adoptively transferred CTL clones can reduce viral titer [18]. Moreover, humans with impaired T cell immunity experience more severe and fatal HMPV infection [6,7,9,19]. Recently, it has been shown that mechanisms exist which drive impairment of the lung T CD8 following HMPV infection in mice and humans [20,21] during primary and secondary infection, further bolstering evidence of the importance of this response in viral control. "
    [Show abstract] [Hide abstract] ABSTRACT: Human metapneumovirus (HMPV) is a major cause of morbidity and mortality from acute lower respiratory tract illness, with most individuals seropositive by age five. Despite the presence of neutralizing antibodies, secondary infections are common and can be severe in young, elderly, and immunocompromised persons. Preclinical vaccine studies for HMPV have suggested a need for a balanced antibody and T cell immune response to enhance protection and avoid lung immunopathology. We infected transgenic mice expressing human HLA-A*0201 with HMPV and used ELISPOT to screen overlapping and predicted epitope peptides. We identified six novel HLA-A2 restricted CD8(+) T cell (TCD8) epitopes, with M39-47 (M39) immunodominant. Tetramer staining detected M39-specific TCD8 in lungs and spleen of HMPV-immune mice. Immunization with adjuvant-formulated M39 peptide reduced lung virus titers upon challenge. Finally, we show that TCD8 from HLA-A*0201 positive humans recognize M39 by IFNγ ELISPOT and tetramer staining. These results will facilitate HMPV vaccine development and human studies.
    Full-text · Article · Apr 2016
    • "The clinical features of hMPV among the two groups showed no differences. Similar results were also obtained by John Williams et al., who found that patients infected with hMPV had varying degrees of immunosuppression, thereby suggesting that severe immune suppression is not a necessary risk factor for hMPV infection [30]. The results also clarified that living in rural regions was more in hMPV positive children than in the other group, and contact with respiratory infected patients was more frequent among hMPV positive children than in the second group. "
    Article · Jan 2015 · Vaccine
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