No cure in sight for clinical syndrome and responsible pathogens

February 1, 2011

In most cases, identification of the pathogen that causes a clinical syndrome brings greater understanding of both the microbe and the spectrum of disease that results from human infection.

The discovery that parvovirus B19 is the cause of erythema infectiosum (fifth disease), for instance, led to a recognition that the same virus also can cause fetal hydrops, aplastic crisis in individuals with sickle cell disease and other hemoglobinopathies, and a febrile illness characterized by a "gloves and socks" rash.

Similarly, we now know not only that human herpesvirus 6 is the cause of the clinical illness recognized as roseola but also that HHV-6 infects virtually every person in the world by age 2 or 3 years and that its reactivation in bone marrow transplant patients can lead to hepatitis, encephalitis, and bone marrow suppression.

Since the discovery of respiratory syncytial virus (RSV) in 1956, a great deal has been learned about the virus, its epidemiology, and the human immune response to infection. We also have learned that bronchiolitis, the clinical hallmark of severe RSV infection, can be caused by a growing list of respiratory viruses. Unlike parvovirus B19 and HHV-6, whose discovery helped explain some poorly understood clinical syndromes, the spectrum of disease associated with RSV and these other viruses remains pretty straightforward. RSV, along with human metapneumovirus, coronavirus, rhinovirus, influenza, parainfluenza viruses, and perhaps as yet unidentified viruses, causes colds, bronchiolitis, and pneumonia.

Effective treatment, however, has been elusive and not straightforward at all. Influenza can be prevented by vaccine and treated with neuraminidase inhibitors, and monoclonal antibody (palivizumab) is effective in preventing severe disease caused by RSV in infants at particularly high risk; but respiratory viral infection continues to be the most common cause of hospitalization for infants in the United States.

In this month's issue, Brian Alverson, MD, and Shawn Leigh Ralston, MD, review the list of symptomatic treatments for bronchiolitis that have gained and lost favor over the past 4 decades.

In addition, they discuss the use of nebulized saline therapy, the most recent addition to that list. Pediatricians, like parents, have a strong desire to find an effective means of relieving the distress of infants with respiratory illnesses. It is this impulse, along with hypotheses that seem reasonable, that have led to the use of corticosteroids, bronchodilators, and ribavirin-all of which have demonstrated only inconsistent benefit.

Some studies of nebulized saline have been reported and others are in progress. Perhaps there will be significant benefit with the addition of this new treatment. The variability with which infants have responded to other therapies, however, suggests that success will be difficult to demonstrate.

DR MCMILLAN Editor-in-Chief Contemporary Pediatrics