Acute respiratory tract infections are amongst the most common pediatric illnesses. Respiratory viruses, such as influenza and respiratory syncytial viruses (RSV), are significant causes of pediatric respiratory distress, bronchiolitis and pneumonia, with each virus underlying an estimated 200–400 deaths per year in the United States in children <5 years of age.1–5
The association between these respiratory infections and weather conditions has been long been appreciated, with epidemiological studies from the Netherlands in the early 20th century demonstrating that upper respiratory tract infections increased as outdoor ambient temperature decreased.6 Colloquially, the winter months are often referred to as the “cold and flu” season in temperate climates.
Various hypotheses, relating to both viral and host factors, have been put forth to explain this epidemicity in temperate climates. Colder weather is thought to affect viral stability, as well as host defenses and behavior. For example, nuclear magnetic resonance data have revealed increased stability of enveloped viruses, such as influenza, with enhanced ordering of phospholipids at lower temperatures.7 Desiccation of airway passages following inhalation of colder, drier air has been shown to affect both ciliary clearance and mucous production, compromising the host’s ability to fight infection.8 The thought that colder weather affects host behavior, the so-called “crowding effect,” argues that lower temperature encourages individuals to spend more time indoors, in closer proximity to one another and in poorly ventilated spaces.9 The basis of this particular hypothesis has been challenged, especially in the context of crowded urban environments and bustling transit systems that continually shuttle masses of people in confined subway cars, for example, in the absence of year-wide epidemics.10 Overall, these factors, amongst others, likely act in concert to influence the seasonality seen with some of the more common respiratory viruses, but they fully account for neither the seasonality of respiratory infections in temperate climates nor the different patterns of viral transmission in tropical and subtropical locations.
Considerable study and attention has been put forth to further elucidate the mechanisms governing respiratory virus epidemicity worldwide. Specifically, environmental factors such as temperature, humidity, UV index, wind and rainfall have been implicated in the seasonality of respiratory virus infections. In this review, we will concentrate on two important pediatric pathogens, influenza virus and RSV, as well as discuss the environmental factors that affect the transmission of other respiratory viruses, such as the rhino-, adeno-, parainfluenza- and metapneumoviruses, which cause significant disease in the pediatric population.
By far, the most research investigating the seasonality of respiratory infections has focused on influenza virus. Recently, large-scale epidemiological studies have demonstrated a relationship between weather conditions and influenza virus transmission, not only in temperate climates, but also in tropical and subtropical regions. In a study analyzing data from 85 countries, Azziz-Baumgartner et al11 observed that the timing of influenza epidemics in temperate climates, as expected, correlates with low temperature. After adjusting for mean monthly sunshine, precipitation, absolute humidity and latitude, peak infection rates were typically observed during or immediately following the coldest month of the year. In contrast, influenza viruses in the tropics tended to circulate year-round or to appear in multiple epidemics in a given year.11 A similar analysis of worldwide, laboratory-confirmed influenza virus infections corroborated these findings.12
Tamerius et al13 also investigated the role of environmental factors in the seasonality of influenza in temperate and tropical climates. Their analyses determined two main climatic conditions associated with influenza virus epidemics: “cold-dry” and “humid-rainy”. In temperate climates, annual peaks in influenza prevalence coincided with the low temperature and humidity of the winter months. In tropical locales, influenza virus circulation peaked during months with high humidity and precipitation, with biannual epidemics being more common in Asia and Central and South America. Influenza seasonality was more difficult to predict in subtropical locations, however. For example, in Senegal (15°N), influenza virus activity peaked during months with high humidity and precipitation, while in Hong Kong (22°N), influenza epidemics occurred biannually, once during the “humid-rainy” summer season and then again in “cold-dry” winter conditions.13 Similar patterns in tropical and subtropical locations were also documented by Bloom-Feshbach et al.12
It is of note that these large epidemiological studies exclude data from the recent 2009 influenza A (H1N1) pandemic virus (pH1N1), which emerged in the Northern Hemisphere during the warm spring and summer months, representing a significant departure from the normal epidemicity of seasonal influenza. In subsequent years, however, pH1N1 circulation has displayed typical winter seasonality and, experimentally, pH1N1 virus transmission has been shown to be enhanced at low temperature and relative humidity.14
To better understand viral seasonality, animal models have been developed to assess how not only temperature, but also humidity, play a role in infection of influenza virus.
In an expansion of earlier work using the mouse model,15 Lowen et al16 were able to demonstrate the effects of temperature and humidity on influenza virus transmission among experimental guinea pigs. In this setting, the efficiency of transmission from infected to susceptible animal, occurring via airborne respiratory droplets, was highly dependent upon the temperature and relative humidity at which the experiments were conducted (Fig. 1).16,17 Transmission of an influenza A (H3N2) isolate was most efficient at low temperature (5°C) and low relative humidity (20–35%), particularly when infected and susceptible guinea pigs were housed in separate cages that prevented direct contact with one another. Further work with influenza A (H1N1) and influenza B isolates found a similar temperature dependence to airborne transmission efficiency.14,18
When guinea pig experiments were conducted at 20°C, virus was transmitted most effectively to naïve animals at low (20–35%) and intermediate (65%) conditions (Fig. 1). These data further our understanding of conditions that are favorable for influenza virus transmission and may mirror the “cold-dry” and “humid-rainy” meteorological conditions appreciated to be conducive to influenza virus transmission in large-scale studies.
It is of note that temperature and relative humidity are intimately related, making the individual contributions of these environmental factors difficult to disentangle. Because warm air can hold more water vapor than cold air, warm air is exponentially “wetter” (ie, has higher absolute humidity) than cold air with the same relative humidity. Mathematical modeling of the experimental data of Lowen et al16 suggests that humidity affects the size of the airborne respiratory droplets that harbor infectious virus particles; in turn, the water content of virus-containing droplets influences how long the virus can remain aloft and are potentially transmissible to a new host. At high humidity, heavy, water-laden droplets are removed relatively rapidly from the air via gravitational settling. Conversely, low humidity favors evaporation of respiratory droplets, forming dry aerosols (also called “droplet nuclei”) that are light enough to float in the air for long periods.15 Identification of relative humidity as a determinant of transmission is likely complicated by its direct relationship to temperature and therefore may not be in fact a pure variable. Further study to tease apart the contributions of these factors is therefore warranted, though absolute humidity has been associated with the seasonal onset of influenza virus infection in the continental United States.19
Respiratory Syncytial Virus
When considering the seasonality of RSV infection in various climates, it is of note that RSV peak infection also varies amongst different locations. Heights of infection have been found to correlate with colder weather in temperate, Mediterranean and desert regions, while precipitation has been identified as a more accurate predictor of infection in tropical and subtropical regions by Weber et al.20 An association between climatic factors and infection in the equatorial tropics was not seen, however.20 In a study comparing RSV infection in temperate, tropical and subtropical climates by Bloom-Feshbach et al,12 RSV infection was found to display seasonality much like influenza virus in temperate climates, with infection rates rising during cold and dry winter months. Peak RSV prevalence, however, was less predictable than that of influenza virus and RSV epidemics were found over a broader timeframe; 22% of RSV outbreaks occurred before December or after March in the Northern Hemisphere. Notably, the timing of RSV circulation was related to geographic location, with regional variations in peak infection.12 Mullins et al21 drew similar conclusions regarding RSV epidemicity, demonstrating that its circulation began earlier and was of longer duration in the South compared with the Midwestern United States, for example. RSV seasons were found to vary not only by location, but also by year over a 10-year period.
RSV epidemics are known to display a different periodicity across various climates. For example, semiannual peaks occur in tropical locations like Taiwan, Hong Kong, Singapore, Malaysia and Colombia, while biennial epidemics were more common in temperate locales. These “long-short” epidemics in temperate climates are marked by a major midwinter outbreak followed by milder disease in the spring of the next year.12,22,23 While alternating outbreaks of RSV serotypes A and B have been put forth as a possible explanation for the periodicity seen,22 this hypothesis is still debated.12
Using weather and infection data from Salt Lake County, UT, Walton et al24 developed probability models to predict RSV outbreaks. Temperature and wind speed were determined to be key variables in these analyses; other environmental factors were also determined to influence RSV infection, although with varied efficacy depending on the amount of lead-time in the analysis.24 Other mathematical models that use data from several geographic locations were unable to relate the time of peak infection with temperature,25 although this may be due to the pronounced variation seen with RSV epidemicity in different locales. It is possible that, in contrast to influenza virus, for example, localized environmental or nonenvironmental factors play a larger role on RSV infectivity. On the whole, however, these data and others underscore the importance of temperature and other environmental parameters in affecting RSV circulation patterns.
OTHER RESPIRATORY VIRUSES
Although large-scale epidemiological data are relatively lacking for other respiratory viruses, some smaller studies highlight the epidemicity of other respiratory pathogens that commonly cause infection in pediatric patients. While some demonstrate a temperate seasonality such as influenza virus and RSV, other viruses are known to cause year-round infections. Human metapneumovirus (hMPV) displays a similar epidemicity to influenza virus, for example, with peak infection in the cold winter months in temperate climates.26,27 Human parainfluenza virus type 1 (HPIV-1) typically causes epidemics in the fall, HPIV-2 in the winter and HPIV-3, the most prevalent subtype, causing year-round infection or springtime epidemics.23,28 While both rhino- and adenoviruses circulate throughout the year, well-documented rhinovirus peaks have been appreciated in the autumn and spring in temperate locales.23 Although some small, primarily single-city or single-country studies have identified certain environmental factors that may contribute to transmission of these common pediatric respiratory viruses, meaningful patterns of seasonality are difficult to appreciate with a paucity of data.
Aerosol viability experiments that measure the contribution of humidity and temperature have demonstrated that paramyxoviruses, such as HPIV-3 and RSV specifically, are most stable at low temperature and humidity,29 although some investigations did report bimodal stability similar to what has been reported for influenza viruses.30 Interestingly, it has been determined that adenovirus isolates are most stable at high relative humidity,29 which is consistent with the findings of du Prel et al26 Continued experimentation is perhaps warranted, as additional tools to study aerosol viability are now at our disposal, more than three decades after the initial publication of these reports. Nevertheless, the identified differences in stability may in fact have biological basis and may be secondary to inherent differences in viral structures. For example, the presence (as for influenza and RSV) or absence (as for adenovirus) of a viral envelope may determine which environmental factors are more or less detrimental to viral stability.7,31
Both laboratory and epidemiological data suggest that temperature plays a large role in the transmission efficiency of these viruses. Of course, temperature alone cannot fully explain the epidemiology of respiratory viruses in all parts of the world, and maximally efficient virus transmission is likely the result of several factors acting in concert, including, but not limited to, host defenses and immunity, virus infectivity and stability, as well as other environmental factors. The information generated to date, however, has broad public health implications. For example, climate and humidity control in hospital units would perhaps be helpful to minimize the spread of virus to others. It has also been suggested that better ventilation of indoor environments would be an appropriate preventative measure against infection.32 While this review focuses primarily on what is presumed to be aerosol transmission of respiratory viruses, it is possible that viral spread via direct contact is playing a larger role than appreciated, especially in tropical and subtropical locations.33 Of course, additional study is warranted to determine maximally efficient interventions that could be executed with minimal cost and difficulty.
Overall, a more detailed understanding of the basis of virus infection would help in formulating and optimizing public health interventions to minimize the health burden of respiratory disease in children and adults. Identification of specific factors that are relevant for a particular virus in a certain geographic location will be of critical importance to best prevent viral spread in a particular community and should be a goal for investigations in the future.
1. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–186
2. Iwane MK, Edwards KM, Szilagyi PG, et al.New Vaccine Surveillance Network. Population-based surveillance for hospitalizations associated with respiratory syncytial virus, influenza virus, and parainfluenza viruses among young children. Pediatrics. 2004;113:1758–1764
3. Hall CB, Weinberg GA, Blumkin AK, et al. Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age. Pediatrics. 2013;132:e341–e348
4. Asner S, Stephens D, Pedulla P, et al. Risk factors and outcomes for respiratory syncytial virus-related infections in immunocompromised children. Pediatr Infect Dis J. 2013;32:1073–1076
5. Geskey JM, Cyran SE. Managing the morbidity associated with respiratory viral infections in children with congenital heart disease. Int J Pediatr. 2012;2012:646780
6. van Loghem JJ. An Epidemiological Contribution to the Knowledge of the Respiratory Diseases. J Hyg (Lond). 1928;28:33–54
7. Polozov IV, Bezrukov L, Gawrisch K, et al. Progressive ordering with decreasing temperature of the phospholipids of influenza virus. Nat Chem Biol. 2008;4:248–255
8. Salah B, Dinh Xuan AT, Fouilladieu JL, et al. Nasal mucociliary transport in healthy subjects is slower when breathing dry air. Eur Respir J. 1988;1:852–855
9. Lofgren E, Fefferman NH, Naumov YN, et al. Influenza seasonality: underlying causes and modeling theories. J Virol. 2007;81:5429–5436
10. Andrewes C The Common Cold. 1965 London Weidenfeld and Nicolson:133–145
11. Azziz Baumgartner E, Dao CN, Nasreen S, et al. Seasonality, timing, and climate drivers of influenza activity worldwide. J Infect Dis. 2012;206:838–846
12. Bloom-Feshbach K, Alonso WJ, Charu V, et al. Latitudinal variations in seasonal activity of influenza and respiratory syncytial virus (RSV): a global comparative review. PLoS One. 2013;8:e54445
13. Tamerius JD, Shaman J, Alonso WJ, et al. Environmental predictors of seasonal influenza epidemics across temperate and tropical climates. PLoS Pathog. 2013;9:e1003194
14. Steel J, Palese P, Lowen AC. Transmission of a 2009 pandemic influenza virus shows a sensitivity to temperature and humidity similar to that of an H3N2 seasonal strain. J Virol. 2011;85:1400–1402
15. Pica N, Bouvier NM. Environmental factors affecting the transmission of respiratory viruses. Curr Opin Virol. 2012;2:90–95
16. Lowen AC, Mubareka S, Steel J, et al. Influenza virus transmission is dependent on relative humidity and temperature. PLoS Pathog. 2007;3:1470–1476
17. Lowen AC, Steel J, Mubareka S, et al. High temperature (30 degrees C) blocks aerosol but not contact transmission of influenza virus. J Virol. 2008;82:5650–5652
18. Pica N, Chou YY, Bouvier NM, et al. Transmission of influenza B viruses in the guinea pig. J Virol. 2012;86:4279–4287
19. Shaman J, Pitzer VE, Viboud C, et al. Absolute humidity and the seasonal onset of influenza in the continental United States. PLoS Biol. 2010;8:e1000316
20. Weber MW, Mulholland EK, Greenwood BM. Respiratory syncytial virus infection in tropical and developing countries. Trop Med Int Health. 1998;3:268–280
21. Mullins JA, Lamonte AC, Bresee JS, et al. Substantial variability in community respiratory syncytial virus season timing. Pediatr Infect Dis J. 2003;22:857–862
22. Waris M. Pattern of respiratory syncytial virus epidemics in Finland: two-year cycles with alternating prevalence of groups A and B. J Infect Dis. 1991;163:464–469
23. Monto AS. Occurrence of respiratory virus: time, place and person. Pediatr Infect Dis J. 2004;23(1 Suppl):S58–S64
24. Walton NA, Poynton MR, Gesteland PH, et al. Predicting the start week of respiratory syncytial virus outbreaks using real time weather variables. BMC Med Inform Decis Mak. 2010;10:68
25. White LJ, Mandl JN, Gomes MG, et al. Understanding the transmission dynamics of respiratory syncytial virus using multiple time series and nested models. Math Biosci. 2007;209:222–239
26. du Prel JB, Puppe W, Gröndahl B, et al. Are meteorological parameters associated with acute respiratory tract infections? Clin Infect Dis. 2009;49:861–868
27. Wang Y, Chen Z, Yan YD, et al. Seasonal distribution and epidemiological characteristics of human metapneumovirus infections in pediatric inpatients in Southeast China. Arch Virol. 2013;158:417–424
28. Wright PFMandell GL, Bennett JE, Dolin R.. Parainfluenza viruses. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Disease. 20097th ed Philadelphia Churchill Livingstone Elsevier:2195–2199
29. Miller WS, Artenstein MS. Aerosol stability of three acute respiratory disease viruses. Proc Soc Exp Biol Med. 1967;125:222–227
30. Rechsteiner J. Inactivation of respiratory syncytial virus in air. Antonie Van Leeuwenhoek. 1969;35:238
31. Minhaz Ud-Dean SM. Structural explanation for the effect of humidity on persistence of airborne virus: seasonality of influenza. J Theor Biol. 2010;264:822–829
32. Li Y, Leung GM, Tang JW, et al. Role of ventilation in airborne transmission of infectious agents in the built environment - a multidisciplinary systematic review. Indoor Air. 2007;17:2–18
33. Lowen A, Palese P. Transmission of influenza virus in temperate zones is predominantly by aerosol, in the tropics by contact: a hypothesis. PLoS Curr. 2009;1:RRN1002
© 2014 by Lippincott Williams & Wilkins, Inc.