A new respiratory virus

July 2002

---Philip A. Brunell, MD

A year ago, a Dutch group identified a new virus, which may turn out to be a significant cause of respiratory illness in young children (Nature Med. 2001;7[6]:719). The etiology of respiratory illnesses in children has been incremental compared to the rapid progress which was made soon after the isolation of poliovirus, the first enterovirus. There were at least two reasons for this. Tissue culture systems were developed to grow poliovirus, which was the initial major concern. These systems did not support the propagation of respiratory viruses as well as they did enteroviruses. The second reason probably related to the greater stability of enteroviruses compared to most respiratory agents. Respiratory agents generally require more care in transport. Laboratory confirmation of clinical diagnosis of respiratory syncytial virus (RSV) accelerated only after the development of the fluorescent antibody (FA) and enzyme-linked immunosorbent assay (ELISA) as isolation was difficult. This facilitated cohorting of hospitalized patients the evaluation of the effects of passive immunization in the clinical trials. Influenza viruses, which long had been a major concern, originally had been grown in embryonated eggs prior to their propagation in tissue culture; the ferret provided a nasty but amenable animal model.

This new agent, which has been identified as a human pneumovirus, commonly infects children. As many as 25% of children between 6 and 12 months and almost all 5-year-olds tested had serologic evidence of infection. In one study it was isolated from 10% of nasopharyngeal isolates and 20% during certain months (Infectious Diseases in Children, June 2002). The authors of this article indicate that it may be a major cause of bronchiolitis although it has been associated with a variety of respiratory illnesses in children. Thus in many respects it resembles RSV to which it is closely related. Both are paramyxoviruses. RSV is the only human representative of the pneumovirus subfamily and this new agent is the only representative of the metapneumovirus subfamily. Thus we might anticipate that the epidemiology and clinical manifestations of these two agents might be quite similar. The cytopathic effect is similar and both have two subtypes.

What does all this mean? One of the first issues is the relative advantage of using an immune globulin derived from the blood of multiple donors and presumably containing antibody against hMPV for the prevention of bronchiolitis rather than using a monoclonal antibody, palivizumab (Synagis, MedImmune), specifically against RSV. It is difficult to determine from the data whether the immune globulin has much of an effect on bronchiolitis that is non-RSV as the numbers in the study are quite small (N Engl J Med. 1993;3.29:1524). What one can glean from this study is that there are a significant number of moderate to severe lower respiratory tract infections that are not due to RSV. Presumably these are due to influenza, parainfluenza and hMPV. There is no clinical evidence that antibody directed against RSV will be protective against hMPV. It will be important to determine the proportion of cases of bronchiolitis attributable to hMPV. If this is substantial it may be worthwhile to develop a cocktail of monoclonals against the human pneumoviruses. Thus it might be possible to prevent a greater number of cases of bronchiolitis. Palivizumab reduces the number caused by RSV by 63%, but there is no evidence to suggest it is effective in preventing non-RSV bronchiolitis.

Although we are told to try to isolate patients who are demonstrated to be infected with RSV, cohorting them is acceptable. In some instances patients with bronchiolitis are cohorted. This could increase the risk of cross-infection of patients with bronchiolitis with another pneumovirus. It gives us added reason to practice careful infection control in the management of these patients. We do have evidence that hMPV infects adults as well as children (J Infect Dis. 2002;185:1600). We now should be better able to tease out those who have unusually severe or persistent diseases as a result of dual infection.

Still to be answered are the questions of response of this new virus to antiviral agents and their contribution to chronic airway disease. One would guess that similar problems would be encountered in developing a vaccine against hMPV as with RSV, but many of the lessons learned from RSV probably will be applicable.

When an agent such as hMPV is newly discovered, is it appropriate to designate it by the trendy title “emerging infection”? This agent is emerging only in the sense that the science has emerged. Antibody has been detected in sera obtained a half century ago. It also is apparent that this virus is ubiquitous as it now has been described in three continents and will undoubtedly be found wherever one looks.