Influenza

Summary review of the 2010-2011 northern hemisphere winter influenza season

This review summarizes the chronology, epidemiology, and virology of the northern hemisphere temperate regions' winter influenza season encompassing the time period from October 2010 through the end of April 2011.

It is an expanded version of the WHO Weekly Epidemiological Record (WER) 27 May 2011, vol. 86 (pp 221-232).
The data presented are primarily derived from reports published by national ministries of health and reported through FluNet. Data sources and references are listed at the bottom of the page.

Summary points

• The winter influenza season in the temperate countries of the northern hemisphere began in late October in Asia, a month later in Europe and North America, but was largely over by the end of April.
• The most commonly detected virus was different in North America, where influenza A(H3N2) and influenza type B co-circulated with influenza A(H1N1)2009, and Europe, where influenza A(H1N1)2009 was by far the most commonly detected virus.
• Although it was no longer the predominant influenza virus circulating in many parts of the world, H1N1 (2009) otherwise behaved much the same way as it had during the pandemic in terms of the age group most affect and the clinical pattern of illness.
• The impact of the influenza season in some areas where H1N1 (2009) was the predominant virus was more than in the previous year, most notably in the United Kingdom (UK) where intensive care units were stressed by large numbers of cases requiring ventilatory support.
• More than 90% of viruses detected around the world were similar antigenically to those found in the seasonal trivalent influenza vaccine.
• Antiviral resistance in influenza A(H1N1)2009 remained at a very low level. There were case reports with no history of exposure to antiviral medications, consistent with some community transmission of resistant virus.

Detailed description

North America:

Active influenza transmission in North America was first noted in tropical and subtropical areas of Mexico in mid to late July 2010. Active transmission in Mexico continued throughout the rest of 2010 and overlapped with the start of the winter season in the temperate areas of the continent in late November. The season in Mexico was essentially over by late January of 2011 however an outbreak of influenza A(H1N1) 2009 was reported in April in the northern border state of Chihuahua associated with a number deaths. In the United States of America (USA), influenza activity first began in the southern states, slightly later in the southwest, and subsequently the northern states. In Canada, active community transmission first began in Ontario and Quebec Provinces and later in the more western provinces. Influenza virus transmission peaked in temperate North America around late January to early February and had returned to national baseline levels by the end of April. Transmission in Mexico was almost entirely associated with influenza A(H3N2) with much smaller amounts of influenza type B appearing later in the season and the above mentioned localized H1N1 (2009) outbreak on the USA border occurring in late April. Influenza A(H3N2) was also the most common virus circulating in the USA and Canada throughout the winter, though the USA had notably more influenza type B and H1N1 (2009) than either of the other two countries. As compared to the 2009-2010 season, the peak proportion of outpatient visits that were due to influenza-like illness (ILI) was lower in the 2010-2011 season for both the USA and Canada; however, mortality from pneumonia and influenza was at or exceeded the epidemic threshold in the USA for a period of 12 consecutive weeks during this season. Hospitalization rates for influenza in the USA were highest in those ≥65 years of age, followed by children 0–4 years of age. Similarly, in Canada, 68% of adult hospitalizations and 79% of adult fatalities were 65 years old or older. Ninety-five children under the age of 18 died in the USA and five in Canada. Influenza type B appeared to be disproportionately associated with severe disease in children, being found in 39% of laboratory confirmed pediatric deaths reported in the USA and 26% of pediatric hospital admissions in Canada compared to 26% and 12% respectively in general population outpatient data. Risk factor data from the USA indicate that among adults hospitalized with laboratory-confirmed influenza the most commonly identified risk factors were cardiovascular disease, asthma or chronic lung disease, and metabolic disorders. Among pediatric patients hospitalized with laboratory-confirmed influenza in the USA, the most common underlying medical condition reported was asthma in about 20% of cases. Overall, of all patients hospitalized with laboratory-confirmed influenza in the USA, 7% required mechanical ventilation and 2% died, slightly less than last year (10% and 3% respectively in the 2009-2010 season).

Europe and the Middle East:

The influenza season in Europe first became evident with a report of large numbers of influenza cases requiring intensive care management in England and Scotland in early December 2010. Within two weeks, countries of the western European continent and the Middle East also began to report increased rates of influenza. Notable transmission occurred slightly later in Eastern Europe. The peak of transmission was seen in late January to early February in Western Europe and two to three weeks later in Eastern Europe. In contrast to North America, influenza A(H1N1)2009 was the predominant virus strain with lesser amounts of influenza type B. Influenza A(H3N2) was relatively uncommon in Europe and the Middle East. The season of 2010-2011 was marked by an increase in the number of influenza-related fatalities in the UK compared to the 2009-2010 season. This was also reflected in an excess in all-cause mortality that was higher than the previous season. Intensive care units reported being pressured by the high numbers of admissions in the UK, Ireland, Greece, and Georgia. While other countries of the continent also reported fatalities and severe cases requiring intensive care management, the magnitude in comparison to last season is uncertain. The risk groups with severe H1N1 (2009) influenza were similar to the previous season. Cases requiring intensive care or dying were more often young and middle-aged adults than is seen in a typical influenza season. In the UK, for example, among 539 fatal cases for which age data are available, only 22% were over the age of 64 years. Sixty to 70% of severe cases had at least one recognized risk factor for severe disease, the most common of which was chronic respiratory disease or asthma. Most severe cases had not been vaccinated against influenza in this season.

Northern Asia:

The 2010-2011 influenza season in the northern temperate areas of Asia began late October to early November and had peaked by the end of December. Transmission in Mongolia and northern China was nearly all influenza A(H3N2) in the early weeks of the season, a continuation of summer time H3N2 transmission occurring primarily in southern China. Influenza A(H1N1)2009 began to be detected by the first week of 2011 in both countries and became the most commonly detected subtype within a few weeks. In the Republic of Korea, the timing of transmission was similar to that seen in Mongolia and China but, in contrast to those two countries, H1N1 (2009) was by far the most commonly detected virus from the beginning of the season, with much smaller numbers of H3N2. In Japan, sustained community transmission began around the same time as the countries of the mainland but peaked a few weeks later in late January 2011. While early transmission in Japan was a mix of H3N2 and H1N1 (2009) viruses, by January, H1N1 (2009) was clearly the predominant virus and remained so throughout the rest of the season. Only small numbers of influenza type B viruses were detected in northern Asia in the 2010-2011 season. Rates of ILI were lower in all countries in 2010-2011 than in the previous season but similar in magnitude to previous years. In Mongolia, the proportion of hospitalizations due to pneumonia and the number of deaths reported due to pneumonia were all less than in the 2009-2010 season. Similarly, a number of severe and fatal cases were reported in China but in lower numbers than the previous season.

Tropical regions:

Most intense transmission in the tropics occurred earlier in the year during the Northern Hemisphere summer; however, some transmission was seen in more localized areas in the tropics. In the Central American region, influenza A(H3N2) was circulating during June and July of 2010 followed by a smaller wave of influenza type B. Later, during the northern hemisphere winter, Brazil, Columbia, Paraguay, Peru, and Ecuador had significant transmission of H3N2 extending from early November 2010 through January 2011. Venezuela, in contrast, was noted to have a large number of cases of influenza A(H1N1) 2009 beginning in late February 2010 and peaking at the end of March.

In western African countries transmission of H1N1 (2009), H3N2 and influenza type B all occurred at different peak times. Mali and Senegal both experienced peaks of H3N2 transmission with smaller amounts of influenza B and H1N1 (2009) in October and November 2010 followed by smaller peaks of H1N1 and type be in February of 2011. Ghana had a relatively large peak of H1N1 (2009) in May through July followed by low numbers of H3N2 throughout the rest of the year and a second peak of H1N1 (2009) in March 2011. In eastern Africa, Kenya and Uganda experienced continuous transmission of influenza throughout the year primarily associated with H3N2 from July through mid December and transitioning to H1N1 (2009) and influenza type B predominance from mid December onwards. Rwanda, in contrast, had very little virus detected until February 2011 at which time H3N2 was noted to be circulating.

India had a peak of H1N1 (2009) transmission in July but transmission was not detected beyond late September. Thailand and Bangladesh had circulation during the same period of time but also had significant amounts of influenza type B co-circulating with H1N1 (2009) later in their seasons. In southern China, H3N2 was the predominant virus circulating during the northern hemisphere summer, peaking in late August to early September, but was then replaced by H1N1 (2009) during the winter. Southern Asia as a whole, however, had relatively little influenza transmission during the northern hemisphere winter months. Notably, Australia reported unusual out-of-season transmission of influenza virus during their summer months, primarily H3N2. This was observed in most jurisdictions but reports were highest in the northern states of Queensland and the Northern Territories.

Antigenic testing:

Ninety-nine percent of the H1N1 (2009) and 96% H3N2 viruses characterized antigenically were related to the strains contained in the current trivalent seasonal influenza vaccine globally in the 2010-2011 season. Approximately 91% of influenza type B viruses were of the Victoria lineage, a small percentage of which had low cross-reactive antibody titres to B/Brisbane/60/2008, and the remainder were of the Yamagata lineage. These proportions did not vary substantially from region to region.

Antiviral sensitivity testing:

More than 98% of the 9,300 H1N1 (2009) viruses tested for antiviral susceptibility by the WHO Global Influenza Surveillance Network (GISN) were found to be sensitive to oseltamivir with some regional variation. All oseltamivir resistance was associated with a substitution of H275Y in the neuraminidase gene. Europe detected more oseltamivir resistance than the USA (3% vs. 0.7% respectively) but many specimens there were selected for testing due to their high risk for having resistance (e.g. from patients on prolonged treatment or with treatment failure). Specimens collected from the community in Europe had rates of resistance closer to 1%. Of note, Europe also had reports of oseltamivir resistant cases with no known exposure to the drug, indicating that some low level community transmission of resistant virus may have occurred. The frequency with which oseltamivir resistance was detected did not appear to increase on either continent during the course of the season. No zanamivir resistance was evident for any of the viruses tested. All influenza A(H1N1)2009 viruses tested by the GISN were resistant to the M2 inhibitors, amantadine and rimantadine due to a S31N substitution in the M2 protein. H3N2 and influenza type B were all sensitive to both oseltamivir and zanamivir except for one isolate of H3N2 with oseltamivir resistance detected in the USA in April of 2011.

Conclusions

Influenza A(H1N1)2009 continues to circulate widely. However in contrast to the pattern observed during the pandemic, the virus is now co-circulating with other influenza viruses and was not the predominant influenza A virus in many countries. Circulation this season occurred during the expected influenza seasonal time frame with no out-of-season community transmission reported in temperate northern countries. The pattern of association between severe disease and age was similar to that observed previously. Influenza A(H1N1)2009 continues to be more of a problem for young and middle-aged adults, while influenza A(H3N2) causes more severe disease in adults over the age of 65 years. Influenza type B appears to disproportionately affect young children. A few countries appeared to have a higher number of severe cases compared to last year for reasons that are unclear. This was most notable in the UK though this observation may well be a surveillance artefact related to the active surveillance for severe disease that was carried out there. All three circulating viruses demonstrated very little antigenic drift over the last year and were closely related to the three strains contained in the seasonal influenza vaccine. In addition, all but a very small percentage of viruses tested remain sensitive to neuraminidase inhibitors. This reemphasises the need to continue to vaccinate and to treat early patients at high risk for developing severe disease, including those at the extremes of age, those with certain chronic medical illness, and pregnant women.


Data sources and references

1. WHO, FluNet
2. WHO Regional Office for the Americas, Influenza Weekly Report
3. Centers for Disease Control and Prevention, FluView
4. Public Health Agency of Canada, FluWatch
5. European Centre for Disease Prevention and Control, Weekly Influenza Surveillance Overview
6. WHO Regional Office for Europe, EuroFlu Regional Influenza Surveillance Report
7. Health Protection Agency (UK), National Influenza Report
8. WHO Regional Office for the Western Pacific Influenza, Situation Updates
9. WHO, Global Influenza Surveillance Network
10. Eurosurveillance, Volume 16, Issue 5, 03 February 2011. Lackenby A, et al. Continued Emergence and Changing Epidemiology of Oseltamivir-Resistant Influenza A(H1N1)2009 Virus, United Kingdom, Winter 2010/11
11. WHO, Guidelines for Pharmacological Management of Pandemic (H1N1) 2009 Influenza and other Influenza Viruses
12. WHO, Recommendations for influenza vaccines

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