Human metapneumovirus was first identified 15 years ago and is now known to cause both upper and lower respiratory tract infection. Young children in particular are susceptible to bronchiolitis and pneumonia due to this virus, and there are approximately 20,000 U.S. children hospitalized each year because of this infection. Clinically, pediatric metapneumovirus infection is similar to both respiratory syncytial virus and influenza virus infections. It had been thought that North American infections with metapneumovirus usually occurred in the winter and spring, but Haynes and colleagues conducted a nationwide epidemiologic review to more specifically understand the seasonality of metapneumovirus in relation to the seasonal patterns of influenza and respiratory syncytial virus.

Hundreds of clinical and public health laboratories contribute tens of thousands of samples to the National Respiratory and Enteric Virus Surveillance System each year. Samples from the most active laboratories were included in this study. Antigen detection and polymerase chain reaction methods were used. The viral “season” was defined as beginning and ending when the percentage of samples positive for a specific virus rose above 3% and then declined below 3%.

The study included 945,836 metapneumovirus tests with 3.6% being positive, 1.8 million respiratory syncytial virus tests with 15.3% positive, and 2.2 million influenza tests with 18.2% positive from July 2008 through June 2014 from 60 laboratories in 30 states. While there were some variations in times of viral activity from year to year, the median active seasons and peak months are noted in Table 1.

Virus

Months in Season

Month of Peak Positivity

Human metapneumovirus

January May

March

Respiratory syncytial virus

November March

January

Influenza

December May

January

Typically, viral activity increases annually first for respiratory syncytial virus, then for influenza, and finally for human metapneumovirus. However, there was some activity of these viruses throughout the years of testing. Interestingly, the human metapneumovirus season shifted forward and back by about one month each year so that alternate years had relatively earlier and later seasons.

COMMENTARY

It is interesting to know when various viruses are “in season.” For respiratory syncytial virus and influenza, knowledge of seasons prompts the timing of vaccination programs. Since there is currently no specific vaccine or curative treatment for metapneumovirus, there is not yet a specific therapeutic change to make based on this understanding of seasonality.

Is testing for human metapneumovirus clinically valuable?

Since there is no specific therapeutic intervention for human metapneumovirus infection, does testing have clinical value (beyond the epidemiologic value of understanding seasons)? This question is especially important since diagnostic respiratory infection “panels” are increasingly available, whereby multiple infectious agents can be sought with a single test panel, for a significant cost.

First, one must be cognizant of the problem of assuming causality when a specific agent is identified in a sick child. A case-control study reported from Sweden last year included preschool-aged children with community-acquired pneumonia and compared them to healthy control children.1 Human metapneumovirus, respiratory syncytial virus, adenovirus, and influenza virus were found significantly more commonly in sick than in well children. Bocavirus and coronavirus were found more commonly in well than in sick children. Enterovirus, parainfluenza, and rhinovirus were found similarly in sick and well children (with rhinovirus found in about one-fourth of all children whether they were sick or not). Simply finding a virus in a sick child does not prove causality, but finding metapneumovirus, influenza, or respiratory syncytial virus is suggestive that it is etiologically related to the illness.1,2

Second, it has been postulated that identification of a potentially causative virus in a sick child might reduce testing and treatment of possible bacterial infection. In a Cochrane review of emergency department-based studies, identification of a presumptive viral cause for a child’s febrile respiratory illness reduced the number of chest X-rays obtained but did not alter antibiotic use.3 However, positive respiratory panel results for viral agents did reduce antibiotic use and length of inpatient stay in hospitalized children in a different study.4

What determines the seasonality of viral respiratory infections?

Seasonality of viral respiratory infections occurs in other parts of the world as well, but the seasons are a bit different. In Hong Kong, influenza A peaks in late January to mid-March but then has a smaller wave of activity from May to early September. There, respiratory syncytial virus has broader consistent activity from late February to mid-September. Interestingly, environmental temperature correlated with the times of influenza and respiratory syncytial virus infection but did not correlate with adenovirus activity. Influenza A was more prevalent during times of low rainfall, but respiratory syncytial virus was seen less during those drier times of the year.5

Controlled animal studies support the link between temperature and humidity, on one hand, and respiratory viral infection on the other.6 Transmission of influenza between guinea pigs depends both on temperature and humidity. Transmission is more efficient in low temperatures (such as 5°C) and essentially blocked at higher temperatures (30°C). Dry conditions were also more favorable toward the spread of influenza than either moderate or high humidity conditions.6 This is consistent with indoor (low humidity) cold weather (low temperature) spread of influenza in humans during winter time. The reasons for this are likely multifactorial, depending both on the virus and the potential hosts. Influenza virus is stable in low humidity and is potentially inactivated at higher temperatures.6 On the host side, cooling of the nasal mucosa inhibits mucociliary clearance.6 In addition, transmission of virus between people depends on droplets; in low humidity, water evaporates from respiratory droplets, making the droplets smaller and better able to stay suspended in the air for transmission over longer distances.6

The humidity of school classrooms varies between schools and throughout days and seasons.7 Charlie Huskins and his colleagues have shown that using classroom humidifiers for four hours can increase humidity enough to potentially decrease viral survival by 30%.7 Perhaps one way to limit influenza transmission would be to humidify indoor spaces during winter time.

Other environmental factors also can facilitate the spread of respiratory viruses. In China, there is a strong positive relationship between high levels of air pollution and the incidence of influenza.8 This relationship held even when the analysis was controlled for humidity and temperature.8

Thus, respiratory virus transmission follows seasonal patterns related to temperature, humidity, and air pollution. Some of these factors are potentially modifiable in specific areas where children are at risk.

REFERENCES

  1. Rhedin S, et al. Respiratory viruses associated with community-acquired pneumonia in children: Matched case-control study. Thorax 2015;70:847-853.
  2. Rhedin S, et al. Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics 2014;133:e538-e545.
  3. Doan Q, et al. Rapid viral diagnosis for acute febrile respiratory illness in children in the emergency department. Cochrane Database Syst Rev 2014;9:CD006452.
  4. Rogers BB, et al. Impact of a rapid respiratory panel test on patient outcomes. Arch Pathol Lab Med 2015;139:636-641.
  5. Chan PK, et al. Hospitalization incidence, mortality, and seasonality of common respiratory viruses over a period of 15 years in a developed subtropical city. Medicine 2015;94:e2024.
  6. Lowen AC, et al. Roles of humidity and temperature in shaping influenza seasonality. J Virol 2014;88:7692-7695.
  7. Koep TH, et al. Predictors of indoor absolute humidity and estimated effects on influenza virus survival in grade schools. BMC Infect Dis 2013;13:71.
  8. Feng C, et al. Impact of ambient fine particulate matter exposure on the risk of influenza-like-illness: A time-series analysis in Beijing, China. Environ Health 2016;15:17.