Editor's note: This paper was posted online prior to publication in print. To expedite publication, the paper was peer-reviewed by a CCJM physician editor.
The unexpected and well-publicized appearance of swine-origin influenza A (H1N1) virus (S-OIV, informally known as swine flu) has both physicians and the general public on edge. The health care system is mobilizing while the world watches to see if S-OIV will become a pandemic or will just fade away, like the swine flu outbreak of 1976.
In this update, written in mid-May 2009, I try to provide an overview of our current understanding of S-OIV, its diagnosis, treatment, and prevention, knowing that the information about the outbreak is being updated almost daily. To stay abreast of the latest developments, physicians should also consult Web sites of the US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO).
IS IT REALLY ‘SWINE’?
An unexpected surge in influenza A cases toward the end of the 2008–2009 influenza season occurring in and around Mexico City alerted health authorities to a type of influenza virus infection that does not commonly affect humans.
In most years, the annual influenza epidemics in the Northern Hemisphere wane by the end of April. S-OIV infection first appeared in Mexico in April 2009 and shortly after in California and Texas.
In the first few days, the specific viral genetic origin of the epidemic was unclear. But genetic analysis of the virus isolated from a patient in California found that this virus was a recent reassortant of previous triple-reassortants of viruses from pigs, humans, and birds, called triple-reassortant swine influenza A (H1) viruses, which have been circulating in pigs for about a decade, and a Eurasian swine influenza virus.1
Through the years, only a few influenza viruses have been successfully transmitted from birds to humans and then to swine.2 It is interesting that exposure to pigs is not a risk factor for infection with the current S-OIV, unlike in prior cases of swine influenza reported in the literature.3,4 Total reported cases of swine influenza in humans numbered only 50 from 1958 to 2005 and 11 from December 2005 through February 2009, but more cases must have occurred that were not readily identified.
The Veterinary Services of Canada announced on May 2, 2009, that a pig farm in Alberta had been infected with the current type of S-OIV. The infection was introduced to the farm by a carpenter who developed symptoms of influenza after a short stay in Mexico. It is reassuring to learn that, so far, the S-OIV causing illness in these pigs has not been transmitted to people living on that farm. The failure of the S-OIV to transmit back to people suggests that it did not come into the human population directly from swine.
AN EPIDEMIC IN MOTION
As of this writing, 2,532 cases of S-OIV have been confirmed in the United States by the CDC in 44 states, and 3 people have died, for a case-fatality rate of 0.11%. Simultaneously, the WHO reported 4,694 confirmed cases in 30 countries, with 53 deaths (a case-fatality rate of 1.1%), and with 48 of the deaths outside the United States occurring in Mexico.
It is unclear which direction this epidemic will take over the next several months. What happens in the annual influenza season in the Southern Hemisphere, which is just starting, and the early features of influenza activity in the Northern Hemisphere starting in September 2009 will indicate how this epidemic will materialize and the prospects of it’s progressing to an influenza pandemic.
While most adults today have some immunity against previously circulating H1 variants, it is not known if cross-reacting antibodies would provide any protection against the current S-OIV. An animal model showed that mice immunized against the neuraminidase of a human influenza A (H1N1) virus were partially protected from lethal challenge with H5N1 virus.5 In that same study, some humans also had serum antibodies that can inhibit sialidase activity of avian H5N1 viruses.
A remnant of the 1918 pandemic?
The two mechanisms by which pandemic influenza occurred in the 20th century were direct transmission of a novel virus and reassortment of avian and human viruses. In the 1918 pandemic, an influenza A (H1N1) virus closely related to avian viruses adapted to replicate efficiently in humans. Reassortment of an avian influenza A (H2N2) virus and a human influenza A (H1N1) virus resulted in the 1957 pandemic, and reassortment of an avian influenza A H3 virus and a human influenza A (H2N2) virus resulted in the 1968 pandemic.6 One could thus consider the current S-OIV epidemic as genetically a remnant or continuation of the 1918 pandemic, but so far it is less deadly.1
What should we be looking for?
Several characteristic features were seen in prior pandemics that we should be looking for in the next few months to better understand the pandemic potential of the current S-OIV epidemic.7
While the severity of prior pandemics varied significantly, they were all heralded by an antigenic shift in viral subtype. Young adults and previously healthy people were disproportionately affected and had a higher-than-expected death rate. This may be explained by partial protection in older people due to antigen recycling. Secondary bacterial pneumonia is believed to have been a significant cause of death in the 1918 pandemic,8 and bacterial pharyngeal carriage rates are higher in younger people.
Pandemic waves smoldered, lasting 2 to 5 years, but the pattern of deaths varied significantly in different parts of the world. For example, in 1968, most deaths in North America occurred during the first pandemic season, whereas most deaths in Europe and Asia occurred during the second pandemic season.9 This may be explained by geographic variation in preexisting immunity, intrapandemic antigenic drift, viral adaptation, demographic differences, or seasonality.
Of importance, influenza viruses that caused prior pandemics were highly transmissible between humans.