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Flu in the 21st Century

Written in collaboration with Brigitte Hurtubise and Sophie Turrell
Flights grounded, business interrupted, animals slaughtered, large gatherings discouraged, and quarantines enacted. Millions of people dead. While this may sound like a nightmare scenario scripted by Hollywood, these events have actually happened — and may again as a result of a flu pandemic.
But it doesn’t take a highly lethal form of flu to have a life-threatening impact. Since 1976, the seasonal flu (the effects of which vary greatly by season) has killed between 3,000 to 49,000 people (1) in the United States every year and as many as 500,000 annually worldwide, according to the Centers for Disease Prevention and Control (CDC) and the World Health Organization (WHO) (2,3).
Ninety percent of deaths from the flu are in persons aged 65 and older (4). In the 2009-2010 U.S. flu season, there were a total of 2,125 deaths from seasonal flu and an estimated 12,000 from H1N1 (5,6) — a number that is comparable to the U.S. yearly death rate from AIDS (7). Every year 25 to 50 million people acquire influenza in the U.S. and 225,000 of them are hospitalized for the illness (8). A recent CDC report suggests that the number of flu cases is higher than expected in several states for this time in the season (9). The flu’s economic impact is also significant, costing an estimated $87 billion annually in the United States, mostly due to lost wages and productivity (10). Clearly, this is not a disease that can be ignored.
Flu pandemics increase the health, economic and societal impact of this illness exponentially. Here’s why: a pandemic is a massive, prolonged, and widespread disease outbreak on the global level. An influenza pandemic occurs when a new influenza virus strain emerges for which there is little or no immunity in the human population, causing illness and spreading easily from person-to-person. Pandemics can be relatively mild, like last year’s HIN1 outbreak, or they can be catastrophic.
The 1918 “Spanish flu” pandemic killed an estimated 50-100 million people worldwide, far more fatalities — soldiers and civilians — than in all of WWI (11). Pandemic influenza viruses often do not follow the seasonal patterns of peaking in December through February in the northern hemisphere and in June through August in the southern hemisphere. Instead, pandemics can peak in both hemispheres during the same time period (12). Nor do they necessarily follow other epidemiological patterns of seasonal flu; last year’s H1N1, for instance, had higher mortality rates in young adults than in older persons (13).
The economic impact of pandemics is much greater than for seasonal strains. Within a few days of the H1N1 influenza being declared a pandemic in 2009, public speculation about the potential impact of the illness caused crude oil prices, industrial metals, and hog futures to drop and sent stock markets tumbling. Schools closed, flights were cancelled, and tourism slowed. In today’s era of globalization, the H1N1 outbreak underscored that an infectious disease is just a jet plane away threatening the health and economies of countries around the world.
Furthermore, flu pandemics are hardly a phenomenon of the past. In fact, a novel pandemic strain of the flu emerges about every 30 years. Just 1 years ago, the 2009 flu season extended far beyond the usual winter months because of the H1N1 2009 pandemic strain, ending instead on August 10, 2010 (14). The virus infected millions and killed thousands, though so far, the death toll is far below what many health experts feared. However, since pandemic flu is known to outbreak in waves, which can be spread over months or years (as was the case with the Spanish Flu pandemic, consisting of four waves from 1918 to 1920, each increasing in lethality) (15), we must remain vigilant.
Small but can be deadly: the H1N1 virus.
Another alarming piece of news came in November 2010, when a woman was hospitalized with H5N1 avian flu in Hong Kong. The strain of H5N1 that is currently circulating is often referred to as “avian flu” because it is occurring in bird populations, killing most of the birds that contract it globally. On December 31, 2010, South Korea confirmed cases of H5N1 in poultry farms in two cities, although so far there have been no human cases reported there (17) . Japan went on high alert in December as several wild birds in different regions were found dead from a virus that appeared to be H5N1 (18).
Tens of thousands of birds have been slaughtered in meat prefectures where outbreaks of the virus have occurred this year (19). In January, 2011, the WHO confirmed four more cases of H5N1 human infection in Egypt. Health experts worry that the virus could enter the human species in the future through bird-to-human transmission most likely in a region of the world where humans and birds live in close proximity (20).
Many developing countries, where these new diseases often originate, have inadequate public health infrastructure and are limited in their ability to respond effectively to a flu pandemic because they lack adequate surveillance capabilities, sufficient numbers of health care workers, laboratories, vaccines, medications, and other resources. Since 1997, there have been 510 human H5N1 cases reported in fifteen countries in Asia, the Middle East, and Africa (21). Indonesia has reported 171 cases, the most of any nation worldwide, and seven countries have had fewer than five reported cases (22). Despite the relatively low-level of human infections, this strain of the virus is worrisome because of its high mortality rate: of the 516 confirmed cases globally, 306 (nearly 60 percent) have died (23).
This is why the recent news from Hong Kong is so worrisome. Fortunately, as of yet, sustained human-to-human transmission has not occurred with this avian flu strain. Scientists monitor circulating flu strains to determine which are the most prevalent in preparation for formulating the next year’s mix for the flu vaccine. According to a recent article in Nature (24), work is now underway to prepare for a possible future resurgence in the H2N2 strain, which circulated widely in the 1950s and 60s.
This year, the primary form of flu in circulation worldwide is the “garden variety” seasonal flu, which in actuality is numerous different strains that change every year. Today, international influenza occurrence is generally low but increasing in Canada and Europe with a recent marked rise in rates in Mongolia, the Republic of Korea, Sri Lanka, Madagascar and Cameroon. In the U.S., flu activity, which typically peaks in late January to February, has risen since the early fall, but there is a lower incidence of the flu this year (particularly the H1N1 strain) than there was last year (25).
However, despite the disease’s severe consequences in some people, the flu is still viewed by many as a fairly mild illness. This year, 1/3 of mothers did not plan to have their children vaccinated and 25 percent of health workers also decided to forgo the flu vaccine, according to an October survey (26). Many people do not get vaccinated, even though it is relatively inexpensive (around $25) and easily accessible in the United States in venues such as pharmacies, supermarkets, doctors’ offices, and hospitals.
Each year’s vaccine protects against the three flu virus strains that experts believe will be most likely to circulate for the season. Those strains included in the 2010-2011 vaccine are well matched to the circulating flu viruses causing illness so far this year (27). While usually only the very young, elderly, and the medically ill die from the flu, it is still important for everyone over the age of 6 months (except those with chicken egg allergies or who have had a severe reaction to previous flu vaccines) to get immunized (28).
In addition to protecting people from becoming ill, vaccination helps prevent the spread of the virus particularly in vulnerable populations who may not be able to obtain the vaccine themselves. Vaccination helps prevent illness which could possibly cause others to miss school, work, be hospitalized or even die. Under the new health care legislation passed this year, the flu vaccine is fully covered as a preventive service for certain population groups by “non-grandfathered” insurance plans.
However, given the flu’s impact, vaccine development and production are in urgent need of innovation. This is reflected in the first goal of the 2010 National Vaccine Plan: develop new and improved vaccines (29). The flu vaccine, the primary strategy for prevention, is manufactured in the same manner as 50 years ago — a process in which chicken eggs, taken from flocks that must be kept biosecure (to ensure they do not become contaminated with avian flu or any other disease), are used to “grow” the virus, which is then either inactivated (in 90 percent of cases) or attenuated (rendering the virus weakened so as to not cause illness, but still elicit an immune response) (30).
This method is slow, taking between 4-9 months to be available for distribution. Additionally, sometimes there can be a lower than expected yield of HA protein (the protein that signals the immune system to respond when attacked by the flu virus), resulting in fewer doses of vaccine initially.

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