As obstetricians we stand at the front line of preventing and treating pandemic influenza A(H1N1). Our pregnant patients who become infected with the H1N1 virus will potentially be more likely than the general population to develop severe disease, to be hospitalized, and to die from complications of the infection. They also will be at high risk of having preterm birth and fetal loss.
All this means that we must take an aggressive approach to therapy, treating women at the time they present with symptoms and being honest with them about their risks. Moreover, we must plan and execute infection control protocols and other nonpharmacologic interventions that traditionally have not been part of our armamentarium.
To be prepared, it is important that we understand influenza—why and how seasonal and pandemic influenza occur, how pregnant women have fared in previous pandemics, and what their outcomes have been thus far in the current pandemic. Most of us know little about influenza, but as we now practice on the front line with patients who are highly vulnerable, we must know more.
Understanding Pandemic Influenza
Influenza viruses are RNA viruses composed of eight separate negative-strand RNA segments that code for 11 viral proteins. These viruses regularly mutate while replicating themselves, altering their genome and shuffling their genes enough each year that our immune systems do not recognize them.
These ongoing genetic alterations are what drive annual epidemics of seasonal flu and are what make the influenza virus so different from the varicella-zoster virus (chickenpox) and other familiar viruses that are not RNA viruses. While infection with the varicella-zoster virus, or vaccination against it, gives most of us immunity for life, we are all susceptible to annual occurrences of seasonal influenza, regardless of how healthy we are.
There are three influenza virus types: influenza A, B, and C. Only types A and B cause infection in humans. Influenza A, which has been associated with most major pandemics and causes about two-thirds of seasonal influenza, is subtyped according to two surface proteins/antigens: hemagglutinin (H) and neuraminidase (N). Viruses with three different hemagglutinin subtypes H1, H2, and H3, as well as neuraminidase subtypes N1 and N2, have been previously associated with infections in humans.
The major natural reservoir for influenza A virus subtypes is the intestinal track of birds, particularly ducks, geese, and other water fowl. A significant number of different flu virus variations are normal flora in the intestinal tract of these birds.
While most viral infections that humans occasionally acquire from the birds are self-limited, some infections can be dangerous. If one is unlucky enough to be simultaneously infected with an avian influenza virus and a human influenza virus, the genes in each of these two viruses can randomly reassort, or rearrange themselves, to form a new virus.
This phenomenon, called reassortment, is one of two possible phenomena that lead to “antigen shift,” which results in immunologically unique viruses that produce pandemic influenza strains.
The other phenomenon that produces intermittent pandemic strains is called adaptation. In this scenario, an avian virus mutates enough over time—particularly with respect to its hemagglutinin molecule—that it becomes able to infect humans and to be easily transmissible from person to person.
The 1918 “Spanish” influenza pandemic produced by an H1N1 influenza virus—the most lethal pandemic in recorded history that was responsible for an estimated 50-100 million deaths worldwide—is believed to have resulted from genomic adaptation. An avian virus mutated enough that it spread from birds to humans and was then transmissible from person to person by common methods of viral spread. An attenuated version of this H1N1 virus then recurred annually for almost the next 30 years.
The 1957 “Asian flu” pandemic, on the other hand, emerged as a result of reassortment. A person infected with the then seasonally recurring H1N1 human virus was simultaneously infected with an H2N2 avian virus, and the genes reassorted to produce a new immunologically unique H2N2 virus. Fortunately, this virus did not contain many of the virulence factors that influenza viruses need to be highly lethal, so the 1957 pandemic was far milder than the 1918 pandemic.
A similar reassortment process led to the “Hong Kong flu” pandemic in 1968. It is believed that a person infected with the then seasonal H2N2 virus became infected with an H3 avian virus as well, generating a new H3N2 virus. Again, this virus was not as lethal as the 1918 virus, and after the pandemic subsided, an attenuated version became the annual seasonal influenza strain.