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Letter
Human Metapneumovirus and
Community-Acquired Respiratory Illness in Children
Diego Vicente,* Gustavo Cilla,* Milagrosa Montes,* and Emilio Pérez-Trallero*†
*Hospital Donostia, San Sebastián, Spain; and †Universidad del País Vasco,
San Sebastián, Spain
Suggested citation for this article: Vicente
D, Cilla G, Montes M, Pérez-Trallero E. Human metapneumovirus and community-acquired
respiratory illness in children. Emerg Infect Dis [serial online] 2003
May [date cited]. Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no5/02-0615.htm
To the Editor: Stockton et al. have reported the detection of
human metapneumovirus (HMPV) by using reverse transcriptase-polymerase
chain reaction (PCR) in patients with influenzalike illness (1).
These authors examined specimens submitted from patients, mainly adults,
during winter 2000–01 and identified HMPV in 2.2% of patients with influenzalike
illness who had tested negative for influenza virus and human respiratory
syncytial virus (HRSV). Although several papers have been published on
HMPV infection in children (2-4), the real impact of
this virus on the health of the pediatric population remains to be determined.
The data we obtained in the present study support the epidemiologic findings
of J. Stockton et al. (1) and reinforce the notion that
HMPV is a human pathogen associated with community-acquired acute respiratory
tract infection (ARTI).
We investigated the occurrence of HMPV in children <3 years of age
with ARTI during two consecutive winter seasons (November 2000–February
2001 and November 2001–February 2002) as part of a study to detect respiratory
viruses (HRSV, influenza A and B viruses, parainfluenza virus types 1–4,
and adenovirus) among the pediatric population. The study population comprised
565 children who were brought to Hospital Donostia, San Sebastián, Spain,
with reported symptoms of ARTI, most of which (>80%) affected the lower
respiratory tract. Of these children, 379 were hospitalized and 186 were
discharged without admission. Hospital Donostia belongs to the public
health system and is the main referral hospital for a population of 9,500
children <3 years of age. More than 97% of hospitalizations of children
in our region occur in this hospital.
Nasopharyngeal aspirates were obtained and processed for cell culture
by using rapid shell vial techniques on the MDCK, A-549, and LLC-MK2 cell
lines. RNA was then extracted from the original samples by using phenol-chloroform
(TRIzol LS Reagent, Invitrogen Corp., Carlsbad, U.K.) and was converted
into cDNA with random primers by using M-MuLV reverse transcriptase (USB
Corp., Cleveland, OH). Nested PCR was performed to detect HRSV, influenza,
and parainfluenza viruses as previously described (5,6).
The remaining cDNA was frozen at -80°C until subsequent use. We tested
for HMPV in all samples that tested negative for the previously studied
viruses, as well as in 100 randomly selected study samples that were positive
for one or more of these viruses. HMPV detection was performed by PCR
by using 5 µL of stored cDNA with primers derived from the F gene under
previously described conditions (7). The PCR product
(450 bp) from the HMPV-positive samples was sequenced in an ABI PRISM
3100 Genetic Analyzer (Applied Biosystems, Foster City, CA).
In 411 (72.7%) of the 565 patients studied, at least one of the initially
investigated viruses was detected. HRSV was found in 313 (55.4%) children,
influenza in 44 (7.8%), parainfluenza in 36 (6.4%), and adenovirus in
32 (5.7%); 14 mixed infections were detected. Of 154 children with a negative
result, HMPV detection was performed in 147 (95.5%), with a positive result
in six children (4.1%). No HMPV was detected in any of the 100 samples
previously positive for the initially studied respiratory viruses. Four
of the six HMPV-positive children required hospitalization: a 7-month-old
boy with pulmonary bronchodysplasia, rhinitis, and fever of 38.4°C (patient
1); a 20-month-old girl with previous obstructive pulmonary disease who
had acute respiratory insufficiency along with generalized hypoventilation,
crackles, wheezing, and radiologic images of air entrapment requiring
bronchodilator administration (patient 2); a 16-month-old girl who had
a febrile syndrome, basal crackles on pulmonary auscultation, and perihilar
infiltrates (patient 3); and an 11-month-old boy with pneumonia of the
upper left lobe (patient 4). The two remaining patients, a 7-month-old
boy (patient 5) and a 9-month-old girl (patient 6), both with upper respiratory
symptoms and clear chest, did not require hospitalization. In all six
patients, outcome was favorable.
Analysis of the amplified sequences showed two clusters of HMPV. The
first was composed of HMPV from patients 1, 3, 4, and 6 (GenBank accession
nos. AY152846, AY152851, AY152850, and AY152847, respectively), and the
second was composed of HMPV from patients 2 and 5 (GenBank accession nos.
AY152849 and AY152848). The similarity among nucleotide sequences in the
same cluster was >95% and oscillated from 86% to 88% when compared
to those from a different cluster. During the second study season, we
observed circulation of both clusters. When we compared these sequences
of HMPV F gene obtained in Spain with those recently described in North
America (7), we found that the sequences of the first
cluster showed >95% similarity with the isolate CAN97-83 (GenBank
accession no. AY145296), and the sequences from the second cluster showed
>95% similarity with isolates CAN98-73 to CAN98-79 (GenBank
accession nos. AY145287–AY145293), connecting the Canadian isolates to
two well characterized groups of HMPV. Our results suggest that in Spain,
as well as in other places in the world (2,7), two major
HMPV groups exist. The severity of the episodes observed varied from mild
upper respiratory symptoms to severe infections requiring hospitalization
for 2–6 days. Overall, as reported by other authors (2,8),
the clinical picture provoked by HMPV was indistinguishable from that
of other respiratory viruses. The fact that HMPV was not detected in any
of the samples from patients also positive for other respiratory viruses
suggests that coinfection is infrequent. The data reported in our study,
obtained during two consecutive winter seasons in a pediatric population
of southern Europe, allow us to estimate that the incidence of moderate
or severe respiratory infections caused by HMPV is low and that the impact
of the other respiratory viruses is considerably greater. Despite these
results, we think that this new respiratory pathogen warrants surveillance.
HMPV appears to be capable of provoking severe infections, and its role
in human respiratory infections is still poorly understood.
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