Rhinovirus Epidemic Marginalizes Swine Flu Pandemic in Sweden, Fall 2009

An unexpected and sudden decline in the spread of swine flu virus (pandemic H1N1 influenza A virus) in week 36 of 2009 (first week of September) as measured by respiratory samples sent to Swedish laboratories occurred in Sweden and some other European countries, declare A. Linde, et al., in their rapid communication titled “Does viral interference affect spread of influenza?” published on October 8, 2009. (1)

When the investigators asked Swedish laboratorians what viruses they found in the influenza-negative samples they received and processed, the answer was unanimous: rhinoviruses dominated, with sporadic findings of other respiratory viruses, such as enteroviruses and adenoviruses.

Rhinovirus. Source: http://upload.wikimedia.org/wikipedia/commons/e/ef/Rhinovirus.PNG; accessed October 11, 2009.		H1N1 pandemic virus (swine flu virus). Source: http://farm4.static.flickr.com/3409/3484985616_960297de84.jpg; accessed October 11, 2009.

Linde, et al., then retrieved all data from one of the dominant laboratories in Sweden, the microbiological laboratory at Karolinska University Hospital in Stockholm. Indeed, they found “there was an increase in the proportion and number of rhinovirus diagnoses roughly in parallel with the decrease of influenza diagnoses.” (1)

Graph depicting proportion of respiratory samples examined at Karolinska University Hospital, Stockholm, containing pandemic influenza A and rhinoviruses, August-September 2009. Source: http://www.eurosurveillance.org/images/dynamic/EE/V14N40/Rhino_Fig2.jpg; accessed October 11, 2009.		Karolinska University Hospital, Stockholm, Sweden. Source: http://upload.wikimedia.org/wikipedia/commons/3/38/Karolinska.sthlm.2006.jpg; accessed October 11, 2009.

Rhinovirus is the most common virus to infect humans and causes at least 50% of common colds. Rhinoviruses are made of RNA and are among the smallest viruses. They grow best in the temperature range 33-35 degrees Centigrade, which is probably why they reproduce so well in human noses (hence “rhino” or nose).

The investigators pondered the meaning of this finding. They note that modeling and prediction of the spread of influenza are important for rational decision making on how to manage epidemics and pandemics. What then is capable of constraining the spread of the influenza virus?

Three well-known elements constrain the spread of influenza: population immunity, climate, and social behavior. Populations exposed to a certain influenza virus demonstrate higher levels of immunity during future visits of the same or a very similar influenza virus, i.e., older people were less affected by the pandemic flu virus of 1918-1919 because they had “seen” the virus earlier in their lives. Dry and cold weather favors aerosol transmission of influenza because the virus becomes stabilized by hardening of the lipid membrane, thus remaining airborne longer and spreading greater distances. Warm and moist weather, by contrast, favors droplet and possibly contact spread and inoculation by contaminated hands appears to become more important than inhaling airborne particles. Social behaviors associated with holiday time usually interrupts the spread of influenza, say Linde et al. (1)

These constraints do not explain the influenza pattern observed in 2009, however. In Sweden, the “spread increased after the end of the holidays, but after four weeks of increasing activity the spread suddenly declined, despite similar weather conditions and social behavior. Limitation by herd immunity induced by the spread that actually took place is possible, but not very likely, as the reported number of infections and of influenza-like disease in total was rather low.” Indeed, the investigators expected to see a substantial peak in swine flu in Sweden in early October 2009, based on the experience from the United States and the United Kingdom, with considerable, though patchy, spread of the virus during late spring and summer, despite a climate unfavorable to influenza.

Something else is going on! Linde, et al. postulate the following:

A simple but likely explanation for the sudden interruption of the spread of influenza could be the increase in the spread of above all rhinoviruses. It is known that a major rhinovirus epidemic always occurs soon after school has started. The virus is spread mainly by contaminated hands, and has not been reported to be climate-dependent. Thus the spread of rhinoviruses may have had an advantage over influenza due to the mild and moist climate. Once a rhinovirus infection has become established, infected cells start producing interferon and other cytokines, similar to those produced by influenza. This immune reaction causes the cells to enter an antiviral state. Though double infections occur, they are probably not common enough to maintain high level spread of both rhino and influenza viruses in the population. 

Linde, et al., note the reason why rhinoviruses have garnered such attention in 2009 and not before is that people with respiratory tract infections who would not normally have visited a physician, did so in 2009 fearing they had pandemic flu. Respiratory specimens collected and processed to assess for the presence of swine flu unexpectedly identified the preponderant rhinoviruses. In normal years, sentinel testing for influenza viruses would not have commenced until week 40, thereby perhaps missing the rhinovirus contribution.

Linde, et al. conclude with a hypothesis, i.e., “a rhinovirus epidemic that occurred after the end of the summer holidays [in 2009] may have interfered with the spread of pandemic influenza during a period with warm and humid climate that decreases spread of influenza by aerosol.”

Furthermore, they suggest:

1. “The epidemiology of influenza should be related to that of other respiratory viruses for improved understanding of the true epidemiological situation.
2. Surveillance of respiratory infections should be conducted throughout the year to create reliable baselines for influenza-like-illnesses and acute respiratory infections, which are useful when a pandemic virus occurs that does not follow the usual pattern of spread.” (1)

Comment: This is refreshing, innovative, stimulating, and intelligence thinking on a grave matter for human population health.

Notes:

1. A. Linde, M. Rotzen-Ostlund, B. Zweygberg-Wirgart, et al.: “Does viral interference affect spread of influenza?” Eurosurveillance, October 8, 2009, Volume 14, Issue 40, Article1. Available at http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19354; accessed October 11, 2009.