Administrative Office
St. Joseph's Hospital Site, L301-10
50 Charlton Avenue East
HAMILTON, Ontario, CANADA L8N 4A6
PHONE: (905) 521-6141
FAX: (905) 521-6142
http://www.fhs.mcmaster.ca/hrlmp/
Issue No. 87
QUARTERLY NEWSLETTER
April 2006
Human Metapneumovirus - An Emerging Respiratory
Virus
Respiratory tract infections are caused by a number of viruses including Influenza A and B, Parainfluenza,
Respiratory Syncytial Virus (RSV), Adenovirus, Rhinovirus and Coronavirus. Although tests are
performed for common respiratory viruses, a significant proportion of specimens do not yield an etiologic
agent. This can be a result of poor specimen quality, wrong timing of the specimen or an unknown agent.
In recent years a number of new agents have been detected including the human metapneumovirus
(hMPV). First identified in the Netherlands in 2001(van den Hoogen et al., 2001) from children presenting
with acute respiratory disease of unknown origin, this virus has been shown to be the cause respiratory
infection throughout the world including Canada (Boivin et al., 2003; Peret et al., 2002).
Infection with hMPV does not appear to induce immunity in either immunocompetent or
immunocompromised individuals as indicated by serological evidence of reinfection with the same strain
or infection with a second viral genotype. More than one strain may circulate concurrently in a given
season and population. Early studies have shown that hMPV is responsible for ~10% of lower respiratory
tract infections in which no other cause of infection was identified and is responsible for 6% of
hospitalizations in children < 3 y.o. with viral RTI. Additional studies have indicated that the prevalence of
hMPV infection may be as high as 25% in patients presenting with RTI.
hMPV appears to be ubiquitous, as both serological studies and RT-PCR detection have been used to
detect infection in many countries including the Netherlands, Canada, Finland, USA, Australia, Japan,
India, Brazil, UK, Hong Kong, and Argentina. Serological studies in Netherlands indicated antibodies to
the virus in 25% of children 0.5-1 y.o., 55% of children 1-2 y.o., 70% of children 2-5 y.o., and 100% of
children by age 5-10 years. An examination of 72 sera (ages 8-99) collected in 1958 showed that the
virus has been circulating in humans for at least 50 years.
hMPV has a similar seasonality to RSV occurring primarily in the winter months and early spring
(Osterhaus and Fouchier, 2003; Peiris et al., 2003). The pathophysiology of hMPV infection has not been
completed elucidated due to the absence of good animal models but it resembles RSV in its clinical
presentation with both upper or lower respiratory tract involvement. Symptoms range from mild upper
respiratory infection and may include fever, myalgia, vomiting, severe bronchiolitis and pneumonia.
Patients may also present with hoarseness, wheezing, dyspnea, conjunctivitis, and otitis media. hMPV
infection has been associated with febrile seizures, rash, diarrhea and altered liver function tests. hMPV
has also been identified as a cause of exacerbations of asthma and secondary bacterial infections such as
otitis media and pneumonia.
Recent data suggests that hMPV infection is not restricted to children. Although hMPV has been shown to
cause severe LRTI in immunocompromised and elderly patients, our understanding of illness in adults is
incomplete. Falsey et al. (2003) looked at adults over two seasons and found that lower and upper
respiratory infections occurred in both young (<40 y.o.) and elderly adults (>=65 y.o.).
There have been reports of dual infections where 70% of children with severe bronchiolitis and positive for
RSV were also positive for hMPV (Semple et al., 2005; Greenshill et al., 2003). These reports suggested
that a dual infection was associated with increased severity of disease, however, other reports have
shown that the incidence of dual infections is rare. In Hamilton we have seen dual infections with
Rhinovirus and Coronaviruses.
The incubation period for HMPV is not well studied however a single documented hospital acquired
infection has been described by Peiris et al. (2003). In this report a child that shared a room for 24 hrs
with another child with symptomatic hMPV infection that was later confirmed to have hMPV and developed
respiratory symptoms 6 days after sharing the room. This report suggested an incubation time of around 5
days and demonstrated that like RSV, infection control measures should be enforced to prevent
nosocomial HMPV infection.
Although only recently identified in 2001, it is clear that hMPV is a significant pathogen. No vaccines or
chemotherapeutic agents are available to treat hMPV infections. Treatment of hMPV infections is
primarily supportive as no clinical data on susceptibility of hMPV to antiviral therapy is available.
Promising in vitro studies have shown that ribavirin and commercially available intravenous
immunoglobulin preparations inhibit hMPV replication.
The virus grows very slowly in cell culture with cells displaying synctial formation only after 10-14 days.
Detection of the virus has primarily been performed using reverse transcriptase PCR (RT-PCR), although
this is not yet available for most clinical laboratories. We have developed two RT-PCR assays for hMPV
and together with a commercially available monoclonal antibody for direct immunofluorescence testing
that has just become available, have diagnosed and confirmed hMPV infections in Hamilton during the
2005-2006 respiratory season.
The Hamilton Regional Virology Laboratory will begin reporting hMPV infections routinely during the next
respiratory season (2006/2007).
References
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Boivin et al., 2003. Emerg. Infect. Dis. 9:634-640.
Falsey et al. 2003. J. Infect. Dis. 187:785-90.
Greenshill et al., 2003. Emerg. Inf. Dis. 9:372-5.
Osterhaus & Fouchier, 2003. Lancet 361:891-2
Peiris et al., 2003. Emerg. Inf. Dis 9:628-33.
Peret et al., 2002. J. Infect. Dis. 185:1660-1663.
Semple et al., 2005. J. Infect. Dis. 191:382-6.
van Hoogen et al., 2001. Nat. Med. 7:719-724.
Astrid K. Petrich PhD
James B. Mahony PhD FCCM
Discipline of Microbiology
Hamilton Regional Laboratory Medicine Program