Risk Communication and ‘Dread Reckoning’

I am starting this blog with a sincere thank you to a science reporter who spoke with me today about influenza A H5N1 and pointed me to some of the data and articles that I comment on today.

I found that I agree with much of the content of Helen Branswell’s 2012 article in Scientific American entitled ‘Dread Reckoning: H5N1 Bird Flu May Be Less Deadly to Humans Than Previously Thought--or Not’. Her title and her content are excellent, particularly her language choice in the first lines of her article that are extremely relevant to risk analysts.

• ‘Dread’ because it is a strong motivator, especially for public health officials whose best interests are likely protecting people from unnecessary suffering via infectious agents.

• ‘Reckoning’ because estimations of risk in the public health context rarely seem to address uncertainties or the quality of the body of evidence and of the inferences supporting the estimate.

• ‘Fear’ because a worldview that microbes are pathogens that will kill us is likely not evidence-based.

• ‘Worst-case scenario’ because ‘a simple math problem’ of estimating risk is simple only if uncertainty, quality of the data and inferences, and distinctions between correlative and causal data are ignored.

She cites the limitations of available data that may overestimate risk by focusing on the most severely affected and the fallacy of assuming those rates are representative of generally healthy populations around the world.

Is the ‘worst-case’ predicted from 2012 being realized in 2024? Some evidence to consider is summarized below.

The World Health Organization compiled evidence of 888 human cases, 463 fatal, for years 2003-2024. Since 1997, 909 human cases from 23 countries were associated with H5N1 (predominantly 2.3.4.4b clade). Thirteen of 28 human cases reported since 2021 are associated with clade 2.3.4.4b. This virus was documented in migratory birds in Africa, Asia and Europe in 2020, and spread to North America in 2021. Some asymptomatic cases were noted, and human symptoms range from no or mild illness to severe pneumonia with respiratory failure, encephalitis, and multi-organ failure.

Ironically, no mention was made by CDC, FDA, or USDA about applying the Tool for Influenza Pandemic Risk Assessment (TIPRA), available for free from the WHO website, before generating their risk communication messaging about avoiding raw milk and raw milk products.

The 8-page joint report on the Preliminary Assessment of Recent Influenza A (H5N1) Viruses dated 23 April 2024 by the Food and Agriculture Organization, the World Health Organization, and the World Organization for Animal Health states the following.

1.       ‘Of the 28 human cases of A(H5N1) detections reported since the beginning of 2021, all were sporadic infections in people exposed to A(H5N1) viruses through direct or indirect contact with infected birds, infected mammals or contaminated environments, such as live poultry markets or other premises with infected animals. Among these cases, there has been no reported human-to-human transmission.’

2.       ‘It is recommended that national authorities fully assess the risk among occupationally exposed persons using active case finding and serologic methods, as well as work with national agencies to understand the exposure and risk from milk and milk products.’

3.       ‘Investigations are ongoing to understand the risk to humans from consuming milk contaminated with A(H5N1) virus.

FAO/WHO continues from point 3 to stress the importance of following ‘safe food practices’. Yet the concluding point that FAO and WHO ‘strongly advise the consumption of only pasteurized milk and to avoid consuming raw milk,’ like the CDC, FDA, and USDA position, is not evidence-based. Consider the evidence in the analyses below.

• Scientific Opinion on the Public Health Risks Related to the consumption of Raw Drinking Milk (2015)

• Nourishing the Human Holobiont to Reduce the Risk of Non-Communicable Diseases: A Cow’s Milk Evidence Map Example (2022)

• Trends in Burdens of Disease by Transmission Source (USA, 2005–2020) and Hazard Identification for Foods: Focus on Milkborne Disease (2024)

At this point, there are more gaps in knowledge and unanswered questions than mechanistic understanding of influenza A H5N1 viral transmission. Perhaps the only certainty is that evidence is grossly incomplete to support the presumption that Influenza A transmission to humans is anything but by direct contact with groups of infected animals.  

Now let’s briefly consider the evidence on cats.

CDC’s journal Emerging Infectious Disease includes an Early Release Article entitled ‘Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024’. The authors report the following.

1.       ‘Ingestion of feed contaminated with feces from wild birds infected with HPAI virus is presumed to be the most likely initial source of infection in the dairy farms.’

2.       Half of a group of 24 cats fed raw milk from infected cows died with antemortem clinical signs including ‘copious oculonasal discharge’ and postmortem pathologies including ‘multifocal meningeal hemorrhages’ in the cerebrum and pneumonia, with damage to lung, heart and all layers of the retina. This information is consistent with respiratory and ocular infection, not gastrointestinal infection.

3.       Brain has been suggested as the best diagnostic sample to analyze for cats, and neurological signs are well documented in cats.

4.       ‘Most cases in cats result from consuming infected wild birds or contaminated poultry products.’

5.       ‘Exposure to and consumption of dead wild birds’ could not be ruled out for the 12 cats who died or the 12 cats who survived consumption of potentially infective raw milk.

6.       One study was cited that provided experimental evidence of transmission of influenza A H5N1 to cats via artificial inoculation (intratracheal) and by feeding cats virus-infected chickens.

A subsequent study ‘Emergence and Potential Transmission Route of Avian Influenza A (H5N1) Virus in Domestic Cats in Poland, June 2023’ determined that contaminated poultry meat was a potential source of transmission for one of 29 cats in this study. The viral sequences from cats appeared highly related to a stork isolate. Infection of tissue culture cells isolated from canine, feline, and human tissues, of course lacking innate and adaptive immune system components including the healthy gut microbiota, was noted for a viral isolate from this study.

Based on nearly three decades considering microbial risk analysis largely for aerosol and ingestion transmission routes, the available data from cats appears insufficient to make any inferences about foodborne transmission of influenza A H5N1 to humans, from contaminated poultry or potentially contaminated raw milk. It appears that contaminated wild or domestic birds likely transmit influenza A H5N1 to respiratory and ocular systems of cats, not to the gastrointestinal tract.

Some uncertainties to consider in closing for today:

1.       Are the viral particles in raw milk samples infectious?

2.       If so, how long do infected cows shed infective virus in their milk?

3.       What ingested doses cause asymptomatic, mild, and severe disease in cats, controlling for inhalation exposures?

4.       At what ingested doses do the antiviral properties of raw milk protect cats from symptomatic infection?

5.       At what doses do innate and adaptive immune systems of healthy humans protect against infection for ingested influenza A H5N1?

6.       At what doses do healthy gut microbiota protect against infection for ingested influenza A H5N1?

Clearly, there is much to learn about transmission of influenza A H5N1. At present, the risk communication messaging from CDC, FDA, and USDA is not evidence-based and ignores uncertainties about the quality of data and inferences.