To me, two things are most striking about influenza (commonly referred to as the flu): 1) there’s always something new about the flu, and 2) it’s always a big health problem with the potential of being catastrophic. But, before addressing these two statements in more detail, let’s briefly review: What is influenza?
Influenza is an infection of the respiratory tract caused by viruses that belong to the Orthomyxoviridae family. The viruses are passed from person to person by coughing or sneezing. The most common symptoms are a sore throat and a dry cough, accompanied by fever, headache, muscle pains, and fatigue. Sometimes gastrointestinal symptoms, such as nausea, vomiting, and diarrhea occur; but the so-called “stomach flu” is usually not the flu at all, but is caused by some other type of virus. In severe or fatal flu cases, pneumonia (with or without a bacterial superinfection) is usually present.
Although influenza viruses are relatively simple creatures—they only have eight genes compared to our 20,000 or so genes. As such, the structure of their protein coat is more complex and ever-changing. They are divided into three types: A, B, and C. Types A and B are the ones that cause annual or seasonal flu epidemics. They typically sicken up to 20% of the population in any given year. Influenza A viruses are also the cause of what is referred to as pandemic flu, which is far less common but considerably more lethal than seasonal flu. Influenza A viruses are found mainly in wild birds, but also in humans, pigs, horses, and even whales. Influenza B viruses circulate widely, but only among humans.
And here’s where it gets really confusing. Influenza A viruses are divided into multiple subtypes, based on two proteins on their surface: hemagglutinin (H) and neuraminidase (N). There are 16 different hemagglutinin subtypes and nine different neuraminidase subtypes. All known subtypes of influenza A viruses, except for two, have been found among birds. A big problem is that influenza A viruses can suddenly mutate, and when a new influenza A virus emerges, a flu pandemic with global effects can occur.
In the 20th century, we had three flu pandemics. Of these, the 1918-1919 Spanish Flu was the most devastating. This pandemic killed 50-100 million people worldwide—more than all the wars of the 20th century combined. Avian flu virus subtype H1N1 was the culprit. In 1957-1958, H2N2 emerged and was responsible for the Asian Flu pandemic. And in 1968-1969, H3N2 triggered the Hong Kong Flu pandemic. These pandemics were caused by influenza A viruses that originated in birds and spilled over to humans.
So far in the 20th century, only one flu pandemic has erupted, taking place in 2009-2010. This pandemic was caused by a variant of the H1N1 virus (dubbed H1N1v), which jumped from pigs to humans, and thus became known as swine flu.
What keeps many public health experts awake at night are influenza A viruses currently circulating in poultry in Asia. While these flu subtypes, such as H5N1, H7N9, and H7N4, have rarely jumped to humans, when they have done so, the mortality rate is startlingly high, often approaching 50% (by comparison, the mortality rate of the 1918-1919 pandemic was only 2.5%).
It should be pointed out that while the next pandemic influenza is a time bomb waiting to explode, seasonal influenza isn’t a trivial health threat. For example, each year, 5% to 20% of all Americans get the flu, and more than 200,000 are hospitalized because of flu-related complications. Between 1976 and 2006, annual deaths associated with seasonal flu ranged from a low of 3,000 to a high of 49,000. In 2018, seasonal influenza was the worst in over a decade, killing 80,000 people in the U.S. In the 2018-2019 season, more than 57,000 flu-related deaths were recorded.
So, one reason there is always something new about the flu is that the virus is constantly mutating or changing. Each and every year, we are challenged by new viral subtypes. This fact leads to a related and very promising development—progress toward a universal influenza vaccine.
Currently, influenza vaccines are concocted early each year by experts based on predictions of what viral subtypes are most likely to cause seasonal flu later in the year, beginning in the flu season in October. For example, the 2019-2020 trivalent (three-component) influenza vaccines contain A/Brisbane/02/2018 (H1N1)pdm09-like virus, A/Kansas/14/2017 (H3N2)-like virus, and B/Colorado/06/2017-like (Victoria lineage) virus. In good years, that is, those years when the predictions turned out to be right, at best a 60% protection can be expected. When the predictions are off, often only 20% protection is achieved.
The goal of developing a universal influenza vaccine is to target all seasonal and pandemic viral subtypes, thereby markedly improving this rather dismal record of efficacy. The good news is that in 2018, a legislative proposal to create a universal vaccine surfaced in the U.S. Congress. (At the same time, Bill Gates announced a $12 million donation to support this goal.) Additionally, in September 2019, President Trump ordered a “vaccine overhaul” that was followed by an announcement of $130 in million funding for seven years for a universal flu vaccine. The equally good news is that several expert research groups are already carrying out phase I clinical trials of such universal flu vaccines.
But as we await the appearance of a universal influenza vaccine—which will likely take a decade or longer—what should you do? First, it’s important to follow your doctor’s advice, which is based on the Center for Disease Control and Prevention’s recommendations for the prevention of the flu: “vaccinate all persons >/ to 6 months of age who do not have contraindications.” The CDC and your local health department provide excellent information to your doctor regarding all the details, including the contraindications to this generally very safe vaccine. And when should you be vaccinated? Now. Health officials fear that seasonal flu will hit early this year and urge Americans to get flu shots before November.
What if you failed to get vaccinated, or you’re among the sizable minority for whom the current influenza vaccine didn’t work? If you develop symptoms of the flu mentioned earlier, you should immediately call your doctor. There are a number of drugs approved for the treatment of influenza. The most commonly recommended treatment is two doses per day of oral oseltamivir (Tamiflu) for five days or a single oral dose of Xofluza (baloxavir marboxil). (Availability of Xofluza is also something new about the flu. Not surprisingly, it is more expensive—about $150 versus $50 for generic oseltamivir.) Above all, don’t delay treatment as these antiviral agents should be administered within 48 hours of symptom onset to be most effective.
