WHY WAS THE 1918 VIRUS SO VIRULENT?

Probably the most intriguing and disturbing part about the Spanish Flu H1N1 was its hemagglutinin. Virologists recently isolated the virus from victims of the 1918 influenza who had been frozen in the Alaskan tundra. The virologists made hybrids of this virus in order to study it—they took the hemagglutinin of the 1918 Spanish flu and joined it with a mouse-adapted influenza strain. They found that the hemagglutinin of the 1918 virus was adapted to recognize both alpha 2,3 and alpha 2,6 sialic acid linkages. So the virus was able to spread rapidly using its alpha 2,6 binding capabilities in the upper airways, and when it got into the lower airways, where people have alpha 2,3 receptors, it was able to replicate rapidly in lung tissue and cause severe hemorrhagic lung disease.

Fortunately, the new H1N1 virus does not have this capacity and is primarily restricted to alpha 2,6 linkages, although it will cause lower airway disease in some infected people.

WHAT HAPPENS WHEN PEOPLE GET THE FLU?

Influenza is not a subtle virus. It enters the host and tries to replicate extensively before an immune response develops. It is then coughed up and transmitted to someone else. The normal human trachea has a sea of cilia that beat continuously throughout our respiratory epithelium, beating at 12 beats/second, 24 hours a day, seven days a week. This system constantly mechanically cleans our airways. But 48 hours after inoculation with nonfatal H3N2 virus, the respiratory epithelium is wiped out, and only goblet cells remain, which are the cells that produce mucus carried by the cilia. Thus, people with influenza readily get secondary bacterial pneumonias.

In fatal cases of new H1N1, typical histologic lesions of primary influenza pneumonia are seen—the alveoli are filled, and type I and type II pneumocyte apoptosis occurs, along with squamous metaplasia of the bronchial epithelium. Hemorrhage occurs throughout the lung tissue, and the respiratory apparatus cannot function. This occurs in only a minority of people who have H1N1 infection—the mortality rate estimate is between 0.1% and 0.01%. So it's a relatively avirulent virus, but it can be severe in certain individuals.

CAN PHYSICIANS RECOGNIZE INFLUENZA JUST BY TALKING TO THEIR PATIENTS?

In the middle of an epidemic, simply talking to people about their symptoms can be diagnostic. Influenza is dissimilar from an upper respiratory infection. Rhinoviruses typically cause a runny nose and a minor sore throat without a fever. Influenza usually has an abrupt onset and is associated with a fever that is often high. Infected people may have a dry cough, a subjective sense of shortness of breath, and severe myalgia, weakness, and general malaise. Some infected individuals also have gastrointestinal symptoms; the upper respiratory viruses do not usually cause diarrhea. Enteric viruses typically cause diarrhea, but influenza viruses can also cause diarrhea, and with H1N1, physicians are seeing a lot of gastrointestinal signs in patients.

Another strikingly different characteristic of pandemic influenza compared with normal seasonal epidemic influenza is the age distribution of the affected population. H1N1 primarily affects young, healthy individuals. People who were born before 1957 while the Spanish Flu virus was still circulating probably have already had experience with this virus and may have acquired some T-cell and even some B-cell immunity related to that exposure. So the older population is perhaps relatively spared from the ravages of this outbreak of H1N1. However, it has been difficult to get the message out to parents and college students about new H1N1 because most people think influenza is something for their grandparents to worry about. But being young and healthy with a good immune system will not protect individuals against H1N1, which is why the vaccine strategy has focused on young people. It does not mean that if you are older you should not get the vaccine when it becomes available. But individuals who are most likely to get H1N1 and develop severe sequelae should receive the vaccine first.