Human metapneumovirus

Children with respiratory infections frequently present to primary care. For doctors the diagnosis and management of these children is often straightforward — most infections are self-limiting and symptomatic treatment with antipyretics is the standard advice. ‘Viral infection’ is medical shorthand for saying the child has a minor illness and will recover without an antibiotic prescription. But parents may be dissatisfied with a diagnosis of ‘it's just a virus’ and their satisfaction with consultation enhanced by a more precise diagnosis and prognostic information about the likely course of the illness.^1,2

Using classical microbiological techniques, such as culture and immunofluorescence, a viral aetiology (for example rhinovirus, adenovirus, parainfluenza, influenza, respiratory syncytial virus [RSV]) has been identified in about 60% of children with respiratory infection. Advances in genetic diagnostic techniques, and in particular the use of polymerase chain reaction, have improved our ability to increase the percentage of children for which we can identify a viral cause for their respiratory infection. A significant recent advance in our understanding of the aetiology of viral respiratory infections in children has been the identification of a commonly acquired, but newly discovered, virus — human metapneumovirus.

Human metapneumovirus was first reported in Nature in 2001 by a virology group from Holland.³ They discovered a paromyxovirus, closely related to avian pneumovirus, in 28 children with respiratory infection. Until their discovery avian pneumovirus, which causes rhinotracheitis in turkeys, was the sole member of the metapneumovirus genus to be identified. The larger subfamily of pneumoviruses include, among other viruses, a major player in respiratory infection in children — RSV. What was especially fascinating about their discovery was the demonstration by serological work on stored blood specimens taken in 1958 (from subjects aged 8–99 years) that human metapneumovirus has been circulating for more than 50 years, and that by the age of 5 years virtually all children have been exposed to the virus.

Since publication of the human metapneumovirus genus various groups from around the world have begun to document the incidence of infection and associated clinical features. Researchers from Tennessee retrospectively examined 248 specimens collected between 1976 and 2001 from children with respiratory infection which had previously tested negative for virus.⁴ Forty-nine (20%) tested positive for human metapneumovirus RNA. They concluded that 12% of respiratory infections in their cohort were attributable to human metapneumovirus.

For most children the virus causes a mild upper respiratory infection. In others an influenza-like illness may result, with fever, myalgia and vomiting. Reports have described bronchiolitis, croup, pneumonia, conjunctivitis, otitis media, febrile seizures, diarrhoea, rash and altered liver function tests following infection. Preterm infants may be more susceptible. Serological evidence of universal exposure suggests that some infections are sub-clinical.

Asthma exacerbations secondary to viral respiratory tract infections and viral associated wheeze in young children commonly present in primary care. A recent Finnish study reported human metapneumovirus in 8% of consecutive children admitted to hospital with acute respiratory wheezing.⁵ In 70% of these children human metapneumovirus was the sole viral agent. Larger studies are required to determine the morbidity resulting from infection in children with asthma, but it is clear that this newly discovered virus has an important role in causing wheeze.

In addition to its close phylogenic relationship, human metapneumovirus resembles RSV in that first infection does not seem to induce persistent immunity. Repeated infections with RSV are common throughout life. Indeed, 5–25% of all upper and lower respiratory infections in the elderly are due to RSV. Despite evidence of universal exposure by the age of 5 years, human metapneumovirus has also been documented to cause respiratory illness in young adults and in the elderly.⁶

The temporal pattern of human metapneumovirus infection is poorly defined. It certainly circulates during the winter, probably without the usual narrow monthly confines of RSV (November to January) and influenza (January to March). But we await descriptions of any seasonal peaks. Co-infection with other viruses may occur and there have been reports of significant worsening of RSV bronchiolitis if human metapneumovirus is present as well. Before the novel coronavirus causing severe acute respiratory syndrome (SARS) was discovered, human metapneumovirus was mooted as a potential causative agent.

Human metapneumovirus is an important cause of respiratory infections in children. Despite the very recent identification of the virus, live attenuated vaccine development is already under way.⁷ Prevention of acquisition and transmission would significantly reduce the burden of childhood respiratory illness in the UK. Meanwhile, the development of near-patient tests will improve diagnostic accuracy of common viral infections in UK primary care and a full description of the clinical course of the infection will aid clinical management. Parents rightly want to know what is causing their child's symptoms and how long they are likely to last. Moreover, making a precise diagnosis of human metapneumovirus infection is sure to increase professional satisfaction among doctors working in primary care.