Since highly pathogenic avian influenza (HPAI) A subtype H5N6 was first reported in people in 2014 there have been 81 confirmed human cases resulting in 33 deaths. Of these 81 cases, 55 (68%) have occurred in 2021–22, mostly in China. These numbers pale in comparison to the millions of birds that have died because of avian influenza this year. In the USA alone, over 40 million birds have died since January 2022, the outbreak being the first detection of HPAI H5 in the USA since 2016. Avian influenza in Europe is also increasing. Between March and June this year, the European Centre for Disease Prevention and Control (ECDC) reported 1182 HPAI H5 detections in birds including 750 poultry outbreaks, up 38% from the same reporting period last year. This increase in HPAI infections, particularly the notable uptick of H5N6 in humans since late 2021, is cause for concern, but not for panic.
The resurgence of H5N6, in the midst of the ongoing COVID-19 pandemic, is opportune as funding and political appetite for disease surveillance have never been so great. Even before COVID-19, there has been sentinel surveillance of influenza for decades, as shown by the WHO Global Influenza Surveillance and Response System (GISRS) celebrating their 70th anniversary earlier this year. The GISRS are credited with developing the Pandemic Influenza Preparedness Framework, which advocated for the sharing of influenza data allowing for timely development of and access to vaccines and other interventions; its involvement in publishing SARS-CoV-2 sequence data contributed to the impressive and rapid COVID-19 vaccine rollout. So, although HPAI viruses pose a substantial threat to public health, it is a threat that we are aware of and can monitor.
It is well documented that genomic sequencing is integral to outbreak surveillance. According to the ECDC, all HPAI H5 viruses in Europe since October 2021 belong to the 2.3.4.4b clade, which has caused outbreaks in Asia in recent years. The 2.3.4.4b clade is widespread and evolving. In this issue of The Lancet Microbe, the authors of a research letter who sequenced samples from live poultry markets in China determined full-length genomes for 19 H5N6 viruses. The results showed that novel reassortment with other H5 viruses was creating strains that were antigenically distinct from the vaccine that is routinely used in the Chinese poultry industry. Such genomic surveillance can inform vaccine updates, reduce reassortment, and prevent spillover events into humans. Whole genome sequencing has also revealed that a novel reassortment of H5 genotypes was recently introduced into Europe and USA, possibly due to the migration of wild birds. It is clear that metagenomic sequencing of human HPAI infections alone will not be enough to prevent more human cases of avian influenza.
The need for a One Health approach in monitoring emerging infectious diseases is well established. In 2004, the Wildlife Conservation Society published the 12 Manhattan Principles that urged global leaders to recognise the link between environmental and public health. Many of the principles, such as “include wildlife health science as an essential component of global disease prevention” and “reduce the demand for and better regulate the international live wildlife and bushmeat trade”, have not been applied. The spillover of SARS-CoV-2 to humans has led to renewed interest in One Health but integrating multiple disciplines into disease surveillance is complex. In medicine, as exemplified by SARS-CoV-2, scale up of clinical diagnostics attracts major investment and government funding, the same cannot be said about animal diagnostics. To close this gap between human and animal health there needs to be cost-effective innovation. An example of such innovation is featured in this issue of The Lancet Microbe: a modelling study that used machine learning to identify 47 previously undiscovered bat reservoirs of betacoronaviruses, with the view that this method could be applied to monitor other potential zoonotic viruses such as HPAI.
The emergence of a novel influenza strain has been, and likely will always be, a pandemic threat. However, by building on past epidemics, taking a multidisciplinary approach, and embracing innovation we can monitor and prepare. The recent increase of avian influenza in humans should be taken seriously. All reported human H5 infections have been in people who had direct contact with birds and, importantly, no human-to-human transmission has been detected. Unlike at the start of the COVID-19 pandemic, this is a threat we can see coming, and a One Health approach is imperative to preventing an influenza pandemic, failure to use what we know is unconscionable.
For more on avian influenza in the USA see https://www.cdc.gov/flu/avianflu/avian-flu-summary.htm
For more on avian influenza in Europe see https://www.ecdc.europa.eu/sites/default/files/documents/ON-7415-AI-report-final.pdf
For more on the Global Influenza Surveillance and Response System see https://www.who.int/news-room/feature-stories/detail/celebrating-70-years-of-the-global-influenza-surveillance-and-response-system
For more on One Health and pandemics see Lancet Reg Health Eur 2021; 9: 100210
For the 12 Manhattan Principles see http://www.oneworldonehealth.org/sept2004/owoh_sept04.html
© 2022 Jim Varney/Science Photo Library