CLINICAL MATTERS

There have been recent news reports of a strain of bird flu that is infecting cows in the US. But the most unusual aspect of this specific outbreak is that some humans may have been infected with this strain of avian influenza from drinking raw (unpasteurized) milk from an infected cow. When scientists fed raw milk from infected cows to laboratory mice, these showed signs and symptoms of influenza. Researchers are now hard at work trying to understand this new route of transmission for avian flu, and whether it represents a significant risk for causing an outbreak among humans in the near future.

The original pandemic virus before it was supplanted by SARS-CoV-2 is still influenza. Over the centuries, influenza pandemics have decimated human populations. One of the worst in history is the 1918 influenza epidemic, colloquially referred to as the Spanish flu, which infected one-third of the world’s population and may have killed up to 100 million people. This pandemic was caused by a strain of influenza A known as 1918 A(H1N1). In modern times, the last influenza outbreak was the 2009 A(H1N1) swine flu pandemic which fortunately was a lot less deadly because of modern treatment and the quick deployment of effective vaccines.

Influenza infects many different animals, including mammals and birds. There are four types of influenza, namely A, B, C, and D. Among these, influenza A is the most likely to cause outbreaks. The subtype of influenza A is determined by the subtypes of two of its major surface proteins, hemagglutinin (H) and neuraminidase (N). There are 18 H subtypes and 11 N subtypes. This gives rise to a huge number of potential combinations. In addition, the H and N genes can reassort and recombine between different influenza A viruses and can give rise to new virus subtypes, similar to the variants seen in SARS-CoV-2. This is why even though both the 1918 Spanish flu and 2009 swine flu are both A(H1N1), they are still considered different strains of influenza.

Seasonal influenza in humans is usually caused by well-known influenza A subtypes such as A(H3N2). Influenza B can also co-circulate during influenza season so at least two influenza A strains and one influenza B strain are included in the flu vaccine. Previous pandemic viruses like 2009 A(H1N1)also still circulate at a low level. Seasonal human influenza virus infections are usually mild and have low mortality rates in young healthy adults. Unfortunately, these can be deadly in unvaccinated elderly people and those with severe comorbid conditions, so these groups should definitely be offered the flu shot before the season starts.

What about bird flu? Also known as avian influenza, this refers to strains of influenza that predominantly infect birds. Avian influenza can have any H type from 1 to 16 and any N type. However, the most common avian influenza strains that can also infect humans historically have been H5N1 and H7N9. H5N1 in particular is of great concern because this strain of avian influenza, when it does affect humans, can be quite deadly with mortality rates of over 50 percent.

Avian and human influenza viruses have different affinities for specific tissues in the human body. Avian influenza viruses bind to a type of receptor on cells that are commonly found deep in the lungs of a human being. Human influenza viruses are more likely to infect cells with different receptors found in the nasal passages and the throat. This is why human influenza viruses stay in the upper airway and are less likely to cause pneumonia. However, because these human influenza viruses are so close to the mouth and nose, they are easier to transmit when someone coughs and sneezes. On the other hand, avian influenza viruses are more likely to attack the lung cells directly, but because these cells are so deep in the body, it is fortunately not easy to transmit these viruses to other people.

The main trade-off for avian influenza viruses when they cross over to humans is that despite causing a lot of damage to the lungs, their ability to infect other people is very inefficient. Humans aren’t easily infected by avian flu from infected birds either and it takes close proximity and frequent contact with birds to actually get the virus into your body. However, once it enters, it can cause very bad pneumonia. These kinds of viruses that cross over and cause severe disease are consequently known as highly pathogenic avian influenza (HPAI). The fear is that if avian flu recombines with human viruses, it can potentially infect both upper and lower airways and be easily transmissible and at the same time highly pathogenic.

This is why the reports of avian influenza potentially using cow’s milk as a vehicle for transmission to humans are so concerning. Scientists have found that the same receptors that avian influenza binds deep in human lungs are plentiful in the udder of the cow. This allows avian influenza viruses to cross over into cow’s milk. In fact, influenza viruses can routinely be detected in milk from infected cows. If avian influenza, instead of trying to go through the usual respiratory route from bird to human (which isn’t been very efficient), goes through infected milk instead, then it may become that much easier for humans to get infected with avian flu. Fortunately, routine pasteurization deactivates influenza viruses and so this is yet another reason to avoid drinking unpasteurized milk. Aside from influenza, pasteurization protects us from diseases like tuberculosis, salmonellosis, listeriosis, brucellosis, and a host of other foodborne bacterial illnesses that can be transferred from cows to humans.

Viruses like influenza and coronaviruses are constantly circulating and mutating because of their ability to infect different animal hosts. This means that there is some low-level transmission going on all the time in these hosts, and the potential for recombination is immense. The One Health approach of the World Health Organization recognizes this interconnectedness, where what is going on in the forests and farms can have profound downstream effects on human health. This is why proven public health measures are so important, and in light of possible milk-borne transmission of avian flu, pasteurization is one of those simple but highly effective means of protecting us from the next pandemic.