Lack of H5N1 influenza diagnostics undermines global pandemic readiness

Experts at FIND are warning that human cases of H5N1 avian flu could be going undetected because of poor surveillance and a lack of diagnostic testing in at-risk groups. Analysis of the diagnostic landscape reveals extensive diagnostic gaps for this subtype of the influenza A virus, leaving the world with little visibility on the scale or scope of current outbreaks and jeopardizing containment measures.

H5N1 is widespread in wild birds worldwide, and now causing outbreaks in poultry and US dairy cows. The US is using its existing flu surveillance systems to monitor for infections in humans. However, there are currently no commercially available diagnostic tests to detect H5N1 specifically – and no known development pipeline to fix this. Since 2003, 900 human cases have been confirmed, with a staggering 50% mortality rate – but it is likely that cases have been under-reported and under-diagnosed in the face of limited testing capacity and the mortality may therefore be overestimated.

With no confirmed cases of human-to-human transmission yet, leaders have a window of opportunity to step up preparedness for possible outbreaks – including urgently filling critical diagnostic gaps.

Nucleic acid-based (molecular) tests are the current gold standard for detection of influenza viruses, being more sensitive than antigen-based testing, but they generally require laboratory infrastructure to support their use. As seen during the COVID-19 pandemic, rapid tests that can provide a result in around 10–15 minutes, without the need for a laboratory or highly skilled technicians, are a critical tool for outbreak containment – even if they are less sensitive than molecular tests. Rapid tests exist that can differentiate between influenza A and B viruses, but these cannot subtype and thus cannot identify H5N1.

“Without comprehensive diagnostics for H5N1, we are pirouetting on the edge of a volcano that is about to erupt,” said Dr Ayoade Alakija, Board Chair of FIND. “The absence of surveillance means we’re increasing the potential of missing the window to contain outbreaks like H5N1 before they escalate into full-blown pandemics.”

Unlike the COVID-19 virus, which had a relatively low fatality rate but spread rapidly, the potential high mortality rates seen with H5N1 to date mean if human-to-human transmission was to occur, it has potential to cause severe disease and death in those infected.

While there is no evidence to suggest that this will occur – WHO has assessed this risk as being low – FIND is working closely with WHO to monitor the landscape of influenza tests, and develop use cases and a target product profile for the tests required. The organization is also preparing to conduct analytical evaluations of existing tests to assess their potential performance in identifying H5N1. This work is being done as part of FIND’s commitment to the 100 Days Mission for diagnostics.

“Quality diagnostics are the first line of defence in identifying and isolating cases to prevent widespread transmission,” said Dr Rick Bright, FIND Board Member, virologist and former head of the Biomedical Advanced Research and Development Authority in the US. “Having just come out of the worst pandemic in a century, the lack of surveillance and investment into R&D of diagnostics, treatments and vaccines is not only shocking but negligent.”

To mitigate the risk of an H5N1 pandemic, experts recommend the following actions:

1. Strengthen surveillance: Enhance global surveillance to monitor bird and animal populations to enhance visibility on how H5N1 is moving and potentially mutating. This includes training the workforce, simplifying reporting systems and making sure modern technologies such as artificial intelligence are being employed to enhance our predictive analytics.
2. Investment in quality and accessible diagnostics: Allocate resources to develop rapid, accurate, and affordable diagnostic tests for highly pathogenic avian influenza including H5N1. These tests should be accessible globally, especially in places where there is an increased risk to humans due to a close interface with infectious animals and food products.
3. Collaborate on treatments and vaccines: Based on genomic surveillance, utilize global collaborations like the 100 Days Mission, which are built on the work done through partnerships like the ACT-Accelerator and WHO i-MCM-net, to ensure that manufacturing capabilities are scalable to meet global demand – with a priority focus on vulnerable populations and low- and middle-income countries.
4. Develop and regularly update pandemic preparedness and response plans: Based on the lessons of COVID-19, where most countries adapted their pandemic influenza plans to respond, countries should be supported to update their plans to include implementable interventions.

Dr Alakija added: “FIND and partners are analysing the current influenza infrastructure to understand where best to invest resources in a ‘no regrets’ policy. We’re not starting from ground zero like we were for COVID-19, but we really need governments to act now and increase diagnostic testing and data sharing, and put systems in place for benefits sharing should the need arise.”