Epidemiology and timing of seasonal influenza epidemics in the Asia-Pacific region, 2010–2017: implications for influenza vaccination programs

Influenza surveillance data from week 1 of 2010 to week 52 of 2017 were extracted from WHO FluNet [12] for each of the 53 countries included in the WHO Eastern Asia, Southern Asia, South-East Asia, and Oceania-Melanesia-Polynesia influenza transmission zones [13]. WHO FluNet is a web-based data collection and reporting tool of the WHO’s Global Influenza Surveillance and Response System (GISRS) first launched in 1997 [14]. The data are provided remotely by National Influenza Centres of the GISRS and other national influenza reference laboratories collaborating actively with the GISRS, or they are uploaded from WHO regional databases. Data are publicly available and updated weekly.

The following data were extracted: numbers of laboratory-confirmed cases for any influenza virus type or subtype, any A (i.e., regardless of the A subtype), A(H1N1), A(H3N2), A not subtyped, any B, B Victoria lineage, B Yamagata lineage, and B not subtyped. Data from countries were included in the analysis if they were available for at least five consecutive years, with each year having ≥100 laboratory-confirmed influenza cases recorded. For each included country, the number of laboratory-confirmed cases was calculated by week for each type and subtype. The latitude and longitude of each country centroid was obtained from the US Central Intelligence Agency World Fact Book [15]. Maps were generated using mapchart [16].

The timing and amplitude of the primary and secondary influenza epidemic peaks in each country were determined as described previously [17]. Briefly, the weekly number of reported influenza cases was divided by the highest weekly number of cases in each season (January to December), representing the peak activity. The annual, semi-annual, and quarterly harmonics obtained from Fourier decomposition were summed to generate a periodic annual function describing the peak of activity and intensity of the seasonality. The timing of the peaks refers to the month when influenza activity reached its maximum value. The amplitude of the peak(s) was used to quantify the intensity of the seasonality. The primary peak was defined as the highest amplitude during the year. The secondary peak was defined as the second highest amplitude, regardless of whether it occurred before or after the primary peak. Timing of the primary peak of influenza virus circulation resulting from this study and WHO vaccination timing recommendations [18] were compared and categorized as appropriate, inappropriate, or uncertain. Vaccination timing was considered appropriate if it was recommended ≤4 months before the primary peak of influenza virus circulation in 2010–2017. This corresponds to an accepted duration of protection from influenza vaccination [19‐23]. Statistical analysis was performed using Stata version 14 (Stata Corp, College Station, TX) and EPIPOI [24].

Influenza surveillance data for 2010 to 2017 were available from FluNet for 28 of 53 countries in the WHO Eastern Asia, Southern Asia, South-East Asia, and Oceania-Melanesia-Polynesia influenza transmission zones. Data from nine countries (Afghanistan, Bhutan, Fiji, Malaysia, Maldives, Myanmar, New Caledonia, North Korea, Papua New Guinea) were excluded from the analysis because the data covered less than five consecutive years with ≥100 laboratory-confirmed influenza cases (Fig. 1). Therefore, the study database included influenza surveillance data for 19 countries. The included countries were distributed from latitude 46°N to 41°S and from longitude 53°E to 174°E, and the overall population was 3.98 billion (96.2% of the total population of the Asia-Pacific region) based on 2015 estimates [25] (Fig. 2). Except for Laos (2011–2017), Nepal (2012–2017), and Pakistan (2010–2016), data for each country covered all years in the study period (2010–2017).

Overall, 711,734 laboratory-confirmed influenza cases were reported in the 19 countries included (Table 1). Due to a high number of cases in China (n = 473,583; 66.5%), most were located in the Eastern Asia influenza transmission zone. Influenza A dominated overall (68.6%; A/B ratio = 2.18) and in each country during the study period. Influenza B was most common in the South-East Asia region (36.3%; A/B ratio = 1.76) and least common in Southern Asia (23.0%; A/B ratio = 3.35).

Strain circulation varied substantially (Fig. 3 and Additional file 1: Table S1). Of the A types, A(H3N2) dominated overall (41.8%), although the dominant A subtype varied among regions and countries. Of the B lineages, Yamagata (9.0%) was more common than Victoria (7.1%) overall, but the lineage that dominated varied by region and country. The proportion of uncharacterized cases (A or B not subtyped) was only 4.6% for influenza A, but 48.8% for influenza B.

Influenza A dominated in all years (range, 55.5–79.3%; A/B ratio = 1.25–3.82 (Table 2). In 2010, after the pandemic year, influenza B represented 39.2% of all cases. The proportion of influenza B was highest in 2012 (44.5%; A/B ratio = 1.25) and lowest in 2013 (20.7%; A/B ratio = 3.82). The Yamagata and Victoria lineages of influenza B co-circulated in all years (Fig. 4 and Additional file 2: Table S2). The dominant B lineage was Victoria in 2010, 2011, 2012, and 2016, and Yamagata in 2013, 2014, 2015, and 2017.

For the northernmost countries (centroid lying latitude ≥30°N: Iran, Pakistan, Japan, China, South Korea, and Mongolia) and countries in the Southern Hemisphere (Australia and New Zealand), the primary peak was in the winter months (i.e., January to March in the Northern Hemisphere and August to September in the Southern Hemisphere) (Table 3 and Fig. 5). For these countries, the amplitude of the primary peak was high (> 100% except in China), while the amplitude of the secondary peak was < 30%.

For the remaining countries (latitude between 30°N and 10°S), the primary peak occurred throughout the year, and the amplitude was generally lower (Fig. 5). The lowest amplitude was 59.0% in Vietnam. Most of the secondary peaks for these countries had an amplitude > 30% (except for Bangladesh, Indonesia, and the Philippines) and occurred between January and March or between July and December (Fig. 5). Nepal and India had distinct influenza virus circulation patterns, in which both the primary and secondary peaks were of substantial amplitude.

In 12 countries (Bangladesh, Iran, Nepal, Pakistan, China, Japan, Mongolia, South Korea, Indonesia, Philippines, Australia, and New Zealand), the WHO-recommended timing of influenza vaccination was within 4 months before the observed primary peaks of influenza in 2010–2017, and thus considered as appropriate (Table 3). For three countries (Cambodia, Laos, and Thailand), the vaccination timing recommendation was more than 4 months before the primary peaks of influenza in 2010–2017, and so was considered inappropriate. The appropriateness of vaccination timing could not be determined for the remaining four countries (India, Sri Lanka, Singapore, and Vietnam) because these countries had two large peaks of influenza virus circulation separated by several months.