Influenza is one of the world’s most prevalent vaccine preventable diseases, responsible for three to five million cases of severe illness and 250 to 500 thousand deaths annually [1]. Over the past 10 years, there has been an increased focus on establishing more robust surveillance for influenza viruses globally with a heavy emphasis on tropical and subtropical Southeast Asia. Resources, including more than $1 billion from the United States government since 2005 [2], have been preferentially applied to Southeast Asia because of the emergence and persistence of avian influenza A (H5N1) and concern that the region is a “hotspot” for the evolution of other influenza viruses [3]. As demonstrated by H5N1 and the 2009 pandemic caused by the A(H1N1)2009pdm virus, investing in prevention and preparedness strategies is essential for all countries in the region. Moreover, given the increasing trend toward urbanization in Asia [4], the resulting evolution of mega cities, and the ease of modern air travel, the spread of a lethal pandemic influenza virus is a very real possibility and cause for continued concern.

Until recently, use of seasonal influenza vaccine was extremely uncommon in Southeast Asia. For example, doses were primarily limited to the private sector or allotted for pilgrims to the Hajj [5]. The emergence of H5N1 and the A(H1N1)2009pdm virus, together with more country-specific data on the burden of disease, may have increased vaccine uptake in some countries, a pattern previously observed among European nations [6]. However, established vaccination guidelines and the extent of vaccine use have not been well documented. Given the shared global priority to improve access and affordability to influenza vaccines globally [7], as well as the 2012 Strategic Advisory Group of Experts (SAGE) on immunization recommendations for seasonal influenza vaccine, [8] our objectives were to compare country-specific published vaccine guidelines to the SAGE recommendations and report seasonal influenza vaccine sales data in Southeast Asia from 2008–2011.

The 10 ASEAN countries differed widely across the economic and health spectrum (Table 1). Two were high income countries, 6 middle income, and 2 low income. Total health expenditures as a percent of gross domestic product did not correlate with income classification. Under 5-year mortality rates were inversely correlated to income, with the highest rates in the low income countries. Geographically, these countries span from 9^o south to 22^o north of the equator. Of the ten countries contacted, nine (90%, all except Brunei) responded to our survey.

The Southeast Asian countries included in our study differ markedly in their demography, country income classification, and economic resources allocated for healthcare. Despite these differences, awareness of the importance of influenza prevention is increasing in the region as demonstrated through established influenza vaccine guidelines and increased influenza vaccine distribution in the majority of countries. Thailand, an upper-middle income country, and Singapore, a high income country, had the highest rate of vaccines purchased in the private sector since 2010. Indonesia, a lower-middle income country, reported the lowest rates of public sector influenza vaccine purchase. For the 10 countries combined, private sector sales during 2010 and 2011 (after the peak of the A(H1N1)pdm09 pandemic) exceeded pre-pandemic sales during 2008. It is too early to know if this positive effect of the A(H1N1)pdm09 pandemic on the demand for seasonal influenza vaccine will continue in future years suggesting a lasting influence. The only country reporting both private and public sector sales, Thailand, exceeded 10,000 doses per 100,000 persons in 2011. For comparison, in the 2010–2011 influenza season in the United States, 163 million doses of influenza vaccine were distributed for a crude rate of 52,312/100,000 [13], [14]. This 5-fold difference in the vaccine rate per capita between the two countries would likely be smaller if the denominator in Thailand were limited to the targeted risk groups. Nevertheless, it translates into 52% population coverage in the United States vs. 10% coverage in Thailand.

Vaccination guidelines varied substantially across ASEAN countries and in only two countries did guidelines reflect current global recommendations. [8] Most countries with national guidelines recommended vaccination of health care workers and elderly persons, consistent with data from Southeast Asia and other regions documenting the need to protect healthcare workers and their patients as well as elderly persons at increased risk for severe influenza [15], [16], [17]. In contrast, only two countries recommended vaccination for pregnant women, WHO’s highest priority risk group, and only three countries recommended vaccination for children aged 6–23 months, perhaps reflecting a need for more evidence on these risk groups in the region or a lack of resources to expand to these important risk groups. A recent study of influenza vaccine in pregnant women in Bangladesh demonstrated a 63% reduction in laboratory-confirmed influenza infections in infants of vaccinated mothers and better outcomes for gestational age and birth weight in infants [18], [19]. Local data on disease burden, seasonality, cost effectiveness, acceptability, coverage, and delivery strategies are needed to inform development and implementation of national vaccination strategies.

Receipt of A(H1N1)pdm09 pandemic vaccine correlated with income classification, in that poorer countries were eligible for donated vaccine and richer countries purchased vaccine. However, receipt of pandemic vaccine generally did not correlate with the scope of a country’s seasonal influenza vaccination policy. For example, Cambodia does not have seasonal vaccination guidelines but received a donation of 2.7 million doses of A(H1N1)pdm09 monovalent vaccine from WHO. In contrast, Vietnam, which has broad influenza vaccination recommendations, opted against using donated A(H1N1)pdm09 monovalent vaccine during the pandemic. The country cited their regulation to perform quality control testing of the vaccines prior to implementation as a rationale for declining the donation.

Despite the widespread adoption of influenza vaccine recommendations, the current amount of vaccine purchased in most countries does not meet the needs of the identified target groups. To address the growing need for more affordable and accessible influenza vaccines during a pandemic, the World Health Organization assisted eleven countries, including three middle income countries in Southeast Asia (Indonesia, Thailand, and Vietnam), in developing their domestic vaccine production capacity [12]. Indonesia’s BioFarma collaborated with Japan’s Biken Institute to develop local capacity. In July 2011, Thailand licensed a locally-produced, live-attenuated monovalent pandemic influenza vaccine and plans clinical trials on a trivalent influenza vaccine. Finally, Vietnam completed the construction of manufacturing plants for H5N1 and H1N1 vaccines in early 2011 and in April 2012 began a Phase I clinical trial for monovalent H1N1 vaccine. Although these countries are still several years away from commercial production of influenza vaccines that could meet regional needs, progress is clearly underway.

In the absence of locally available, affordable vaccine, lower income countries wanting to introduce vaccine have few options. In 2012, Lao PDR accepted 375,000 doses of seasonal influenza vaccine donated by Walgreens Corporation, a U.S.-based company [20]. This vaccine initiative represents an innovative new public-private partnership, the first of its kind in Lao PDR and perhaps a model for other countries in the region.

Our study has several limitations. First, because private sales data were only provided in aggregate for several countries, disparities in sales between these countries may have been hidden. Second, vaccine sales data are not the same as vaccine uptake as not all vaccines end up in a person’s arm. We did not account for vaccine wastage which would result in lower per capita rates. Third, our rate calculations did not account for the fact that children may have received two doses and this would have decreased the rates. Fourth, we did not limit the denominators to the target groups which would have increased the rates. Finally, private vaccine sales were underestimated because only three multinational vaccine manufacturers were surveyed; the Thailand FDA data are evidence of this.

We provide a summary of national influenza guidelines and influenza vaccination sales for ASEAN countries. Although vaccination sales remain generally low, consistent with global findings [21], we document a regional change towards increased vaccine sales. Advances in local vaccine production capacity in the coming years may further increase regional availability of vaccine. Public funding will be essential for national influenza vaccine programs to continue to develop and grow in Southeast Asia. Only Singapore and Thailand have vaccine recommendations that are consistent with global standards, suggesting that more work is needed to inform policy makers of data which support these important global recommendations.