Human metapneumovirus grows slowly in a limited number of conventional cell cultures, such as tertiary monkey kidney cells (tMKC), rhesus monkey kidney cells (LLC-MK2), and African green monkey (Vero) cells. Growth in these cell lines is trypsin dependent. Variable cytopathic effects including rounding of cells and cell destruction with or without the formation of syncytia have been reported (van den Hoogen et al. 2001; Peret et al. 2002; Boivin et al. 2002; Deffrasnes et al. 2005; Tollefson et al. 2010). HMPV’s slow and unreliable growth and nonspecific cytopathic effects make routine cultures suboptimal for routine diagnosis of infection.

Reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal aspirates or swabs is the most reliable method to establish the diagnosis of hMPV infection. Up to 2/3 of specimens positive for hMPV by RT-PCR may be negative by culture (Ebihara et al. 2004). Multiplex platforms that allow for the simultaneous detection of several respiratory viruses have the advantage of providing specific results with a rapid turnaround time and are commercially available (Freymuth et al. 2006; Mahony et al. 2007). Other methods for diagnosis include enzyme immunoassays (Fuenzalida et al. 2010) and direct and indirect immunofluorescence (Ebihara et al. 2005; Vinh et al. 2008; Landry et al. 2005, 2008; Jun et al. 2008).

The clinical signs and symptoms of hMPV infection are nonspecific and overlap with those of other acute respiratory tract infections. Respiratory syncytial virus is more common than hMPV and is also seen in young children, with a mean age which is slightly younger than hMPV. Infections by other viruses, including adenovirus, coronavirus, and rhinovirus, may present similarly. Influenza must be considered in the differential diagnosis in both children and adults. The cytoplasmic inclusions in epithelial cells, macrophages, and multinucleated giant cells described in one study of bronchoalveolar lavage must be differentiated from those caused by other viruses, such as parainfluenza virus, measles, and RSV (Vargas et al. 2004).

No specific preventive methods are known for hMPV. Respiratory infection control measures to restrict exposure, as well as frequent use of alcohol hand rubs and hand hygiene, have been successful in containing or preventing outbreaks in hospitalized patients (Degail et al. 2012; Cheng et al. 2007).

Treatment of hMPV infection is largely supportive. Severe infections may require oxygen therapy or mechanical ventilation in young children and adults with other comorbidities as well as the elderly. Acute respiratory distress syndrome (ARDS) and death have been reported (Boivin et al. 2007; Schlapbach et al. 2011). Rare reports of successful outcomes in immunosuppressed patients with hMPV pneumonia treated with ribavirin and immunoglobulin have been published (Bonney et al. 2009).

No vaccine is yet available for human metapneumovirus. Animal studies have demonstrated that immunization with inactivated hMPV results in an aberrant immune response with more severe disease upon subsequent hMPV infection (Hamelin et al. 2007), analogous to the experience with children immunized with formalin inactivated RSV (Kim et al. 1969; Kapikian et al. 1969). Therefore, live inactivated hMPV virus vaccines are unlikely candidates for future development.

Other approaches being explored take advantage of the highly conserved and immunogenic F surface protein which has been reported, in some animal studies, to give rise to neutralizing and protective antibodies against both (A and B) lineages (Skiadopoulos et al. 2004, 2006). These include the use of chimeric, live attenuated vaccines, such as bovine/human chimeric parainfluenza virus type 3 expressing hMPV F protein (Tang et al. 2005) or hMPV/avian MPV C chimera (Pham et al. 2005). Recombinant hMPV vaccines lacking the G and/or SH genes or the M gene (Biacchesi et al. 2004, 2005; Buchholz et al. 2005) or component proteins such as soluble hMPV F protein (Herfst and Fouchier 2008; Cseke et al. 2007) have shown promising results in animal studies. These and other vaccination strategies await further studies and trials in human subjects.

hMPV causes acute respiratory infections, ranging from mild upper respiratory infections to severe bronchiolitis and pneumonia. Severe infections are more common in children younger than 2 years of age, the elderly, and the immunosuppressed. Diagnosis depends on identification of the virus in nasopharyngeal swabs or aspirates most commonly by RT-PCR or antigen detection methods. The pulmonary pathological changes of hMPV infection have not been extensively described but include acute and organizing diffuse alveolar damage. Treatment of hMPV is supportive and there are no specific preventive measures.