Bird flu: The science, risks and the road to preparedness

Headlines around the world suggest that bird flu has the potential to become the next influenza pandemic; therefore, it’s essential to understand the risks and the preventative measures being implemented.

To do so, Global Access Diagnostics discusses why we should be concerned about bird flu and what the world is doing to develop a rapid antigen test (RAT), which will support early diagnosis and surveillance.

Types of bird flu viruses

Influenza viruses (also known as bird flu) are classified into four types: A, B, C, and D. Both types A and B circulate widely within the human population, causing seasonal flu, with type A being associated with global pandemics.

Influenza type C, characterised by a single primary surface glycoprotein, is considered antigenically stable and is detected less frequently, typically causing mild infections. In contrast, influenza D primarily affects cattle and is not known to infect or cause illness in humans.

Further evolution of influenza A and B

Influenza B (IBV), with no known animal reservoirs, has diverged into two phylogenetic lineages which co-circulate within the human population, causing approximately 25% of seasonal bird flu cases.

Influenza A circulates globally in both avian and mammalian hosts. As a result of this broad gene pool, 130 influenza A virus (IAV) subtype combinations have been identified.

Highly pathogenic AIV (HPAIV) can cross the species barrier from birds to mammalian species and cause sporadic human infections and/or fatalities.

However, to date, they have not been shown to have the ability for sustained person-to-person transmission. On occasion, though, a variant subtype can cross from pigs to humans.

Human preparedness for a global influenza pandemic

HPAI, as a transboundary zoonotic disease, impacts not only poultry, animal, and human health but also the broader communities worldwide by threatening livelihoods, agricultural productivity, economies, and ecosystems.

Among the AIV HP subtypes of most concern are H5Nx and H9N2 AIVs. These are considered to have the greatest potential to cause a global influenza pandemic, as they are widely prevalent in avian production and exhibit a receptor binding shift towards a human-like preference.

The World Health Organization maintains a list of all candidate vaccines for panzootic bird flu. Currently, there are no indications that the avian influenza viruses currently circulating differ antigenically from proposed candidate vaccine viruses for pandemic preparedness.

Vaccination strategies to control panzootic outbreaks

While some countries, such as China and France, vaccinate poultry, the United States Department of Agriculture (USDA) has approved field safety studies for vaccine candidates designed to protect dairy cows from H5N1. However, many countries, including the UK, follow a no-vaccination policy for disease prevention or control.

The rationale being that current available vaccines have disadvantages, in that although they can reduce mortality, some vaccinated birds may be capable of onward transmission and negatively impact export trade.

Vaccination alone is not a sufficient strategy and requires an integrated approach that includes surveillance. Here, a practical, accessible and affordable rapid antigen test would prove helpful to a)  identify a pan AIV infection, and if present, determine if H5N1 clade 2.3.4.4b or other H5, H7 and H9 subtypes.

On-farm lateral flow tests for bird flu

For both AIV virus antigens and sero-positivity tests, enzyme-linked immunosorbent assay (ELISA) and lateral flow immunochromatographic assay (LFIA) can be deployed.

While ELISA requires a laboratory processing environment with dedicated equipment and a level of technical skill to operate, it allows large numbers of samples to be screened simultaneously.

Some large poultry producers recognise the value of routine screening for infectious diseases and antibody immune responses to vaccination, and have invested in facilities to deploy ELISA tests with trained staff. For most, however, this technology is unobtainable.

LFIAs, on the other hand, being accessible, affordable and easy to use, can readily be adopted on-farm by users with and without scientific expertise, to test poultry either at the individual level or at scale.

Whilst ELISA and LFIA cannot offer the specificity and sensitivity of RTPCR for the diagnosis of bird flu infection, they can provide producers with an affordable and accessible tool to support on-farm monitoring of flock health.

Challenges facing the development of sustainable on-farm AIV tests: Can they be overcome?

LFIAs for the detection of bird flu are commercially available for use with a range of poultry samples, including cloacal secretions, faecal and tracheal /oropharyngeal samples.

However, the limitations of use are numerous and range from in-country legislation surrounding its use, an inability to distinguish between HP and LP AIVs, or to determine the subtype.

Additionally, there is a limited understanding of end-user knowledge regarding the sample type to test for the poultry species concerned, the impact of environmental parameters, and viral persistence in samples, as well as diagnostic test performance.

Whilst there are LFIAs on the market that claim to identify a Pan AIV infection, those that discriminate between H5, H7, and H9 subtypes are considered to lack the desired sensitivity required for early intervention as part of a disease management strategy.

Global Access Diagnostics, in collaboration with The Pirbright Research Institute, is working together to mitigate this issue and develop a suite of first-generation rapid LFIA tests for the poultry industry to detect AIV in the sample matrices described, with a limit of detection (LOD) in the region of <1000 AIV plaque-forming units/ml.

If present, selectively identify whether an H5, H7, or H9 AIV is present. The H5 test is specifically designed to include recognition of the circulating HP H5Nx subtypes, including H5N1.2.3.4 b. A second generation of tests to incorporate a DIVA H5 AIV and other poultry diseases, to include Newcastle disease virus (NDV) and Infectious bronchitis.

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