By Ramsey Hachem, M.D.
Washington University School of Medicine Barnes-Jewish Hospital
Division of Pulmonary and Critical Care
November, 2005
In 1918, perhaps the most lethal pandemic the world has encountered spread from the United States into Europe and the rest of the world, aided by military deployments at the height of World War I. Young, healthy people fell ill one day and often died violently within 24 hours. Their family members were also too sick and could not care for them; whole households fell prey to the outbreak while friends and relatives were either too sick or too scared of becoming sick to help. Hospitals rapidly became inundated and overcrowded. Doctors and nurses were overwhelmed and frequently became victims of the disease themselves and died. The pandemic challenged and humbled the modern world and modern science and medicine. Before it faded in 1920, the disease killed somewhere between 20 and 100 million people worldwide at a time when the world’s population was substantially smaller than it is today. By comparison, it killed more people than the Black Plague in the Middle Ages and many more than AIDS has in the past 25 years. It was influenza, the flu. Influenza remains a serious pathogen today threatening immunocompetent and immunosuppressed people worldwide.
Influenza is a virus like HIV (human immunodeficiency virus), the coronavirus that causes SARS (severe acute respiratory syndrome), and rhinovirus or adenovirus which, among many others, cause the common cold. In many ways viruses are different from what we normally think of as life forms. They are not metabolically active, but their only purpose is replicating. Yet they can’t do so independently. They have to infect others and introduce their genetic information into the infected animal or person’s cells, turning them into factories of thousands of other viruses. Different viruses infect different cell types. For instance, rhinovirus, a cause of the common cold, infects cells lining the respiratory tract and causes runny nose, cough, and congestion. On the other hand, enterovirus infects cells lining the gastrointestinal tract and causes diarrhea and vomiting. The immune response to viral infections causes commonly recognized symptoms of many viruses such as fever, malaise, body aches, etc. Respiratory viruses include influenza (types A and B), parainfluenza, respiratory syncytial virus (RSV), adenovirus, rhinovirus, and others.
When infected by one of these viruses, people typically have symptoms of cough, congestion, and runny nose. Influenza often causes more severe systemic symptoms including high fever, headache, confusion, body aches, and extreme exhaustion. And in addition to infecting the upper respiratory tract, influenza, parainfluenza, and adenovirus can sometimes cause pneumonia especially among immunosuppressed and elderly patients and RSV can cause bronchiolitis in children, an illness characterized by cough, wheezing, and breathlessness. In fact, it has been recognized that infection with RSV early in life may predispose children to developing asthma. Furthermore, people with chronic lung disease are particularly susceptible to viral infections because of their abnormal underlying lung structure and limited respiratory reserve.
Lung transplant recipients are also vulnerable to respiratory viral infections. Because of chronic immunosuppression, they are more likely to acquire a viral infection and more likely to have serious complications as a result of such infections. In the acute setting, viral infections may directly cause a severe illness but also further weaken the local lung defenses against bacterial infections. Furthermore, weeks to months after a respiratory viral infection, lung transplant recipients are at increased risk of developing chronic rejection. While this association has been recognized for the past several years, the biologic mechanisms that result in the onset of chronic rejection after a viral infection remain unclear. In fact, a prospective clinical trial is currently underway to better elucidate these mechanisms and find potential opportunities for therapeutic interventions that might reduce the risk of chronic rejection after a viral infection.
Unfortunately at this time, there is no specific therapy for most respiratory viral infections other than supportive care. There are, however, multiple antivirals that are active against influenza, but their benefit is greatest when started very early after the infection. A few antivirals have proven efficacious against RSV infection in children, but their results have been disappointing for adults. Prevention of an infection remains the best approach. For influenza, a vaccine is available and is effective. Patients are inoculated with a dead or attenuated influenza virus and mount an immune response against the virus so that when they are confronted with the live virus they have an established immunity against it. Unfortunately, transplant recipients often mount an ineffective immune response to the vaccine because of their immunosuppressive therapy and remain poorly prepared to handle an infection. Lastly, no vaccine is currently available for adenovirus, parainfluenza virus, RSV, or rhinovirus. The most recent threat to everyone is an outbreak of bird flu in Europe and Asia. This particular strain appears to be very virulent and painstaking work is currently underway to develop a vaccine.