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CIDRAP- Study: China's complex flu-season patterns pose challenges

Shiloh

Editor, Senior Moderator
Source: http://www.cidrap.umn.edu/news-pers...s-complex-flu-season-patterns-pose-challenges


Study: China's complex flu-season patterns pose challenges
Filed Under:
Influenza Vaccines
Lisa Schnirring | Staff Writer | CIDRAP News
|
Nov 19, 2013

As China moves toward developing a national flu vaccination program, health officials will face a timing challenge, because the northern and southern parts of the country have different seasons, with some areas in between showing two annual flu activity spikes, researchers reported today.

According to an analysis of 7 years of flu activity, flu in northern provinces peaks in January and February, as in other Northern Hemisphere locations, while flu in the southern provinces peaks in the spring. The timing is important for flu vaccination planning, because a key strategy is to immunize people a few weeks before local flu activity ramps up to maximize the temporary protection afforded by flu shots.

The study group included researchers from the Chinese Centre for Disease Control and Prevention (China CDC) and Cecile Viboud, PhD, with the National Institutes of Health (NIH) Fogarty International Center in Bethesda, Md. Their findings appear today in PLoS Medicine.

Vaccine use expected to grow

Flu vaccination has increased in China since 1998, but coverage is still low?about 2%, according to the authors. However, the country's health officials expect use of flu vaccine to rise alongside rapid economic development. The authors said the goal of the study was to help China CDC get a better handle on flu's seasonality and strain circulation in different parts of the country, along with a clearer picture of the factors that drive virus activity.

The researchers collected weekly reports of lab-confirmed influenza A (H3N2) and B from sentinel hospitals in 30 Chinese provinces from 2005 through 2011, excluding the 2009 H1N1 pandemic months. They also compiled data on population size and density, mobility patterns, socioeconomic patterns, and daily weather for the cities in the flu surveillance network.

Then they applied spatiotemporal models to sort out the seasonality of the two flu strains, what factors affect seasonality, and where the broad epidemiologic regions are located in China.

They found that China has three regions with distinct influenza A seasons: the north with its winter peak, the south with its spring peak, and provinces at intermediate latitudes that have two peaks, one in January and February and one in the summer.

The most intriguing finding was a different seasonality for influenza B in China, which predominated in colder months throughout the country, the group wrote.

The researchers noted that China's roughly north-to-south flu spread seems to resemble that of Brazil, another large country that has diverse climates.

No single climate factor stood out as the main flu driver in China, but the team found that minimum temperature, hours of sunshine, and maximum rainfall seemed to influence winter, spring, and more complex patterns.

Multiple vaccination seasons

Concerning the implications for vaccination programs, northern China would follow the timing recommended for the Northern Hemisphere, and vaccination in the country's southernmost provinces would occur mainly in February and March, somewhat similar to the timing used in Southern Hemisphere countries, the authors wrote. They added that better surveillance is needed in the provinces between those two areas to help flesh out where they fall along the timing and locations spectrums.

The group pointed out two main limitations of their study: a short surveillance period and spotty surveillance information from some southern and mid-latitude provinces.

Cecile Viboud, PhD, one of the study coauthors and research scientist at the NIH's Fogarty Center, told CIDRAP News that one of the other surprising findings was semi-annual flu activity around Shanghai, despite its relatively high latitude, which would typically suggest a winter pattern. "There may be local factors specific to China that we don't yet understand," she said.

India is another large country with diverse climates that would be interesting to explore with a similar research design, Viboud said. "Influenza surveillance is still pretty limited there but there is good evidence that seasonal patterns vary in different regions of this large country."

Though the new H7N9 virus in China shows some signs of increased activity during colder months, it is still a zoonosis, and scientists still know very little about its ecology in avian reservoirs, Viboud said, adding, "A head-to-head comparison of the seasonality of human flu versus avian flu would be very interesting."

To build on the new findings, she said the researchers plan to do more detailed geographic analyses at the city level, especially in China's mid-latitude regions that have more complex flu season patterns, she said. The same group will also compare the genetic and antigenic match between the strains circulating in China and the World Health Organization's vaccine recommendations.

China CDC has many competing infectious and chronic disease priorities, she said, adding that her colleagues and China are committed to setting up a national flu immunization program sometime in the years ahead.

The geography of influenza B

In a commentary that accompanied the study, Steven Riley, PhD, with the MRC Centre for Outbreak Analysis and Modelling at Imperial College London, wrote that one of the study's other striking findings was that the proportion of influenza B increased from 20% in the northern provinces to nearly 50% in China's southern provinces. He said the difference adds another challenge to vaccination program design and should prompt phylogeographical and serotype studies of influenza B in China.

The decision to synchronize vaccination programs in southernmost China with the Southern Hemisphere timetable is tempting, but might be premature, Riley wrote. "Genetic data from even a small subset of the viral isolates used for this study could give a definitive picture of the ancestral relationship between viruses circulating in southern China relative to viruses in northern China and Southern Hemisphere populations," he said.

He commented that the diverse flu circulation patterns in China and other countries may lead to a refinement of the current practice of selecting two sets of vaccine strains each year, and that the growth of vaccine programs in regions that straddle the two hemispheres might provide settings to explore the benefits of more rapid vaccine production and locally driven strain selection.

Yu H, Alonso W, Feng L, et al. Characterization of regional influenza seasonality patterns in China and implications for vaccination strategies: spatiotemporal modeling of surveillance data. PLoS Med 2013 Nov 19;10(11):[Full text]

Riley S. Complex disease dynamics and the design of influenza vaccination programs, commentary. PLoS Med 2013 Nov 19;10(11):[Full text]
 
Re: CIDRAP- Study: China's complex flu-season patterns pose challenges

[Source: PLoS Medicine, full page: (LINK). Abstract, edited.]


Research Article

Characterization of Regional Influenza Seasonality Patterns in China and Implications for Vaccination Strategies: Spatio-Temporal Modeling of Surveillance Data

Hongjie Yu, Wladimir J. Alonso, Luzhao Feng, Yi Tan, Yuelong Shu, Weizhong Yang, C?cile Viboud

Published: Nov 19, 2013 / DOI: 10.1371/journal.pmed.1001552


Abstract

Background

The complexity of influenza seasonal patterns in the inter-tropical zone impedes the establishment of effective routine immunization programs. China is a climatologically and economically diverse country, which has yet to establish a national influenza vaccination program. Here we characterize the diversity of influenza seasonality in China and make recommendations to guide future vaccination programs.


Methods and Findings

We compiled weekly reports of laboratory-confirmed influenza A and B infections from sentinel hospitals in cities representing 30 Chinese provinces, 2005?2011, and data on population demographics, mobility patterns, socio-economic, and climate factors. We applied linear regression models with harmonic terms to estimate influenza seasonal characteristics, including the amplitude of annual and semi-annual periodicities, their ratio, and peak timing. Hierarchical Bayesian modeling and hierarchical clustering were used to identify predictors of influenza seasonal characteristics and define epidemiologically-relevant regions. The annual periodicity of influenza A epidemics increased with latitude (mean amplitude of annual cycle standardized by mean incidence, 140% [95% CI 128%?151%] in the north versus 37% [95% CI 27%?47%] in the south, p<0.0001). Epidemics peaked in January?February in Northern China (latitude ≥33?N) and April?June in southernmost regions (latitude <27?N). Provinces at intermediate latitudes experienced dominant semi-annual influenza A periodicity with peaks in January?February and June?August (periodicity ratio >0.6 in provinces located within 27.4?N?31.3?N, slope of latitudinal gradient with latitude −0.016 [95% CI −0.025 to −0.008], p<0.001). In contrast, influenza B activity predominated in colder months throughout most of China. Climate factors were the strongest predictors of influenza seasonality, including minimum temperature, hours of sunshine, and maximum rainfall. Our main study limitations include a short surveillance period and sparse influenza sampling in some of the southern provinces.


Conclusions

Regional-specific influenza vaccination strategies would be optimal in China; in particular, annual campaigns should be initiated 4?6 months apart in Northern and Southern China. Influenza surveillance should be strengthened in mid-latitude provinces, given the complexity of seasonal patterns in this region. More broadly, our findings are consistent with the role of climatic factors on influenza transmission dynamics.

Please see later in the article for the Editors' Summary


Editors' Summary

Background

Every year, millions of people worldwide catch influenza, a viral disease of the airways. Most infected individuals recover quickly but seasonal influenza outbreaks (epidemics) kill about half a million people annually. These epidemics occur because antigenic drift?frequent small changes in the viral proteins to which the immune system responds?means that an immune response produced one year provides only partial protection against influenza the next year. Annual vaccination with a mixture of killed influenza viruses of the major circulating strains boosts this natural immunity and greatly reduces the risk of catching influenza. Consequently, many countries run seasonal influenza vaccination programs. Because the immune response induced by vaccination decays within 4?8 months of vaccination and because of antigenic drift, it is important that these programs are initiated only a few weeks before the onset of local influenza activity. Thus, vaccination starts in early autumn in temperate zones (regions of the world that have a mild climate, part way between a tropical and a polar climate), because seasonal influenza outbreaks occur in the winter months when low humidity and low temperatures favor the transmission of the influenza virus.


Why Was This Study Done?

Unlike temperate regions, seasonal influenza patterns are very diverse in tropical countries, which lie between latitudes 23.5?N and 23.5?S, and in the subtropical countries slightly north and south of these latitudes. In some of these countries, there is year-round influenza activity, in others influenza epidemics occur annually or semi-annually (twice yearly). This complexity, which is perhaps driven by rainfall fluctuations, complicates the establishment of effective routine immunization programs in tropical and subtropical countries. Take China as an example. Before a national influenza vaccination program can be established in this large, climatologically diverse country, public-health experts need a clear picture of influenza seasonality across the country. Here, the researchers use spatio-temporal modeling of influenza surveillance data to characterize the seasonality of influenza A and B (the two types of influenza that usually cause epidemics) in China, to assess the role of putative drivers of seasonality, and to identify broad epidemiological regions (areas with specific patterns of disease) that could be used as a basis to optimize the timing of future Chinese vaccination programs.


What Did the Researchers Do and Find?

The researchers collected together the weekly reports of laboratory-confirmed influenza prepared by the Chinese national sentinel hospital-based surveillance network between 2005 and 2011, data on population size and density, mobility patterns, and socio-economic factors, and daily meteorological data for the cities participating in the surveillance network. They then used various statistical modeling approaches to estimate influenza seasonal characteristics, to assess predictors of influenza seasonal characteristics, and to identify epidemiologically relevant regions. These analyses indicate that, over the study period, northern provinces (latitudes greater than 33?N) experienced winter epidemics of influenza A in January?February, southern provinces (latitudes less than 27?N) experienced peak viral activity in the spring (April?June), and provinces at intermediate latitudes experienced semi-annual epidemic cycles with infection peaks in January?February and June?August. By contrast, influenza B activity predominated in the colder months throughout China. The researchers also report that minimum temperatures, hours of sunshine, and maximum rainfall were the strongest predictors of influenza seasonality.


What Do These Findings Mean?

These findings show that influenza seasonality in China varies between regions and between influenza virus types and suggest that, as in other settings, some of these variations might be associated with specific climatic factors. The accuracy of these findings is limited by the short surveillance period, by sparse surveillance data from some southern and mid-latitude provinces, and by some aspects of the modeling approach used in the study. Further surveillance studies need to be undertaken to confirm influenza seasonality patterns in China. Overall, these findings suggest that, to optimize routine influenza vaccination in China, it will be necessary to stagger the timing of vaccination over three broad geographical regions. More generally, given that there is growing interest in rolling out national influenza immunization programs in low- and middle-income countries, these findings highlight the importance of ensuring that vaccination strategies are optimized by taking into account local disease patterns.


Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1001552.

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