Sentinel minutes for week #17/2024

Pandemic Risks

Highly pathogenic avian influenza (HPAI) H5N1

What a week! The news, data, and analyses are coming in fast and furious.

Overall, ALERT team members feel that the risk of an H5N1 pandemic emerging over the coming decade is increasing. Team members estimate that the chance that the WHO will declare a Public Health Emergency of International Concern (PHEIC) within 1 year from now because of an H5N1 virus, in whole or in part, is 0.9% (range 0.5%-1.3%). The team sees the chance going up substantially over the next decade, with the 5-year chance at 13% (range 10%-15%) and the 10-year chance increasing to 25% (range 20%-30%).

The ALERT team forecasts the chance that a pandemic H5N1 would have a case fatality rate (CFR) of >=10% with medical treatment would be 63% (range 45%-75%). The case fatality rate is a measure of the fraction of people with symptoms who die of a disease, and it is different from the infection fatality rate. The team notes that in a high-CFR pandemic, medical care would probably not be available for many to most people, so that an “effective CFR” would probably be substantially higher.

Sequence data from HPAI H5N1 infections in cattle, one dairy farm worker and other animals on dairy farms were released this week and are starting to paint an increasingly alarming picture. Initial analyses of these data strongly suggest that H5N1 is likely spreading among cattle following a single introduction into cattle from birds, most likely in December or January; a more precise estimate of when such a jump might have occurred is not possible without knowing how quickly flu viruses mutate in cattle. This would fit with dairy farms in Texas seeing drops in milk production over the past 2-3 months. That the virus has likely been spreading in cattle after a single introduction from birds is huge news. Here are some of the implications:

  • H5N1 flu is a new disease that could become endemic in cattle. Flu viruses have not previously been considered to be a major risk to cattle, but an avian flu strain has now jumped directly into cattle. At least some cattle have been reported to have mild respiratory symptoms, loss of appetite, sometimes fever, and reduced milk output by dairy cows.
  • While cattle so far seem to suffer little from H5N1 infections, if the disease is later detected in beef cattle, there could be substantial repercussions for the US beef industry if other countries were to shun imported US beef. The US FDA has said that initial studies indicate that pasteurization inactivates the virus in milk, so there is likely little risk to the US dairy industry. If the disease spreads to other countries, their beef industries could likewise be affected.
  • Because the disease is spreading efficiently among cattle, it will be much harder to stop than if cattle were mainly or only catching it from birds. Cattle H5N1 is spreading northward quickly (see map here). However, it’s also clear from milk sampling in the US that the virus is already widespread in cattle in the US; the virus has been found in 1 out of 5 milk samples from throughout the US. This raises the risk of its geographical spread to other countries, including some with little to no biosurveillance; indeed, given how long it has been spreading, cattle flu could already be spreading undetected in multiple countries. The efficient spread of H5N1 among cattle also raises the risk of its spread to other livestock species. Pigs are a host species of particular concern for human pandemic risk because pigs are susceptible to both avian and human flu viruses, and coinfections with more than one flu strain can lead to the emergence of new, reassortant strains that mix genetic material from the parent strains. This is exactly how the last flu pandemic started in 2009. The good news is that it took decades (see Figure 1) for the last pandemic flu virus to evolve in pigs. The bad news is that H5N1 could be different. The USDA is monitoring feral swine to look for H5N1; the virus has not been detected in feral swine.
  • Figure 1 from Smith et al, 2009. Shaded boxes represent host species; avian (green), swine (red) and human (grey). Coloured lines represent interspecies-transmission pathways of influenza genes.
  • One human H5N1 case in a dairy farm worker is documented. The sequence data strongly suggest that the person caught H5N1 from a cow and that the human virus and the known cattle virus samples are descendants of a single virus jump into cattle. Moreover, the human H5N1 sequence data suggest that there may have been another lineage of cattle H5N1 early on that might have since died out. These data also suggest that H5N1 probably jumped from birds into cattle in Texas. Cattle flu might not be in Mexico—yet.
  • It is possible that substantial numbers of dairy workers could be contracting H5N1 from cattle. If this is really happening, it would imply that our notions of the H5N1 CFR may be substantially too high. Alternatively, dairy workers at affected farms might be sick with common human pathogens, including human flu viruses, RSV and SARS-CoV-2. It will be important to conduct seroprevalence studies to determine how common human infections with H5N1 really are.
  • Another evolutionary branch of HPAI H5N1, a mammalian-adapted H5N1, is emerging in South American sea lions. One scientist has proposed an extremely interesting hypothesis that when sea lion colonies are infected, individuals die and are scavenged by sea birds, which then fly, infected, to the next sea lion colony, and that as those birds die, they are scavenged by sea lions, which then become infected with the virus, transmit it among themselves, and die off and are scavenged by sea birds. In this way, “mutual scavenging” between seabirds and sea lions appears to be spreading H5N1 and allowing a mammalian-adapted evolutionary branch of H5N1 to develop in sea lions. While all mammalian-adapted H5N1 poses some risk to humans, such strains probably pose substantially lower risk to humans overall than does cattle flu.

Can HPAI spread by wind? A recent study suggests that up to 24% of HPAI H7N4 spread from one poultry farm to another, within a 25-km radius, could be due to wind. If such a spread can occur, that could make it even harder to control cattle influenza.

A bat H9N2 influenza virus with pre-pandemic features was found: The bat-borne influenza A virus H9N2 exhibits a set of unexpected pre-pandemic features

Psittacosis cases were recently seen in Argentina and Europe:Cases of psittacosis, a zoonotic bacterial infectious disease also known as “parrot fever,” are always worth taking note of, but the small number of cases seen recently likely reflect low overall risk.


The US passed a foreign aid bill, giving aid to Ukraine, Taiwan, Israel, and Gaza, among other countries: The funding bill was passed by Congress and signed into law by President Biden, along with a bill that could effectively ban TikTok in the United States. These aid packages will likely have profound effects on the courses of the wars in Ukraine and Gaza; the foreign aid law also provides funds for humanitarian aid for Gaza. Arms support given to Taiwan will bolster Taiwan’s defense against potential future aggression from mainland China. Taiwan was very appreciative of the military support, but China was not pleased.

Ukraine used longer-range US missiles for the first time: The longer-range version of the Army Tactical Missile Systems (ATACMS) was secretly provided to Ukraine this month, and these missiles are starting to be used against Russian targets. Such munitions will help Ukraine but probably won’t change the course of the war.

Russia didn’t like NATO drills in Finland: Russia claimed that NATO military drills in Finland are provocative and could lead to conflict. However, Russia has called NATO drills provocative in the past, so the probability that a catastrophe might result from this is exceedingly low.

Russia vetoed a UN vote on stopping the arms race in space: This veto follows on the heels of warnings by the US that Russia is likely developing nuclear weapons for deployment in orbit. Nuclear weapons in space would pose a substantial risk to humanity – including through the perhaps less-discussed risk of Kessler Syndrome, a hypothetical snowballing collision of space debris.

The UK plans to increase defense spending: The UK joined a growing list of European countries pledging to increase their defense spending to counter risks posed by an “axis of authoritarian states with different values to ours.” The country plans to increase defense spending to 2.5% of GDP by 2030, above the NATO guideline of 2.0%.

Macron warned that, “Europe could die”: Macron warned that economic and military pressures could weaken and fragment the EU.

Belarus says it thwarted attack on capital by drones launched from Lithuania

Israel intensified strikes on Rafah ahead of threatened invasion

US Secretary of State Blinken went to China: Blinken visited China for the second time in less than a year, to engage in dialogue to reduce the chance of “miscalculation and conflict.”

A US military base in Syria was attacked: A rocket fired from Iraq struck an American base in Syria. Recent American reprisals have meant that US bases have had something of a respite over the past couple of months, so it is interesting that one was attacked – and, moreover, this attack confirms that Katib Hezbollah, an Iranian proxy, is resuming its attacks. However, the attack will almost certainly not lead to an escalation between the US and Iran in a way that would involve the US attacking Iran proper.


A $100B Microsoft supercomputer? Microsoft’s CTO called speculation about a $100 billion supercomputer “amusingly wrong” but confirmed that Microsoft has ambitious plans.

New NVIDIA servers are out: NVIDIA CEO Jensen Huang personally delivered the first DGX H200, a new, improved server, to Sam Altman and Greg Brockman at OpenAI’s offices.

The LLama 400b model is being trained: The new model looks very similar in performance to GPT-4, based on benchmarks on one of their model checkpoints

Augment, a Co-Pilot rival, launched: The new coding platform, backed by Eric Schmidt, launched on April 24, 2024.

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