Most practitioners know that the flu vaccine has been proven to reduce the frequency of middle ear infections, sinusitis, and pneumonia. However, how that happens is not as clear. My group has been studying the details of the interaction between flu virus and pneumococci to unravel the steps in the dance between the flu virus and the pneumococcus in the nasopharynx that results in significant respiratory diseases. Pneumococci live in the posterior part of the nose and upper pharynx as commensal bacteria in all of us, harmlessly present in relatively low numbers. The bacteria are so common that studies to detect pneumococci in the nasopharynx discover their presence in up to 80% of infants and young children, and about 20% of adults at any one time. The bacteria are harmless in patients that have a competent immune system unless an intercurrent viral upper respiratory infection (URI) occurs.
The trigger in pathogenesis of pneumococcal infections is a viral URI, and particularly influenza infection. The combination of pneumococci and flu in the nose can cause compromise in all four aspects of host defense: 1) structural change, 2) physiologic change, 3) innate immunity change, and 4) adaptive immunity change. Structural change is swelling of the nasal passageways, Eustachian tube, osteomeatal sinus pathway, and tracheobronchial tree. Physiologic change is increased mucus production and reduced cilia beat, resulting in stasis of thickened mucus in the respiratory tree. Thus the stage is set for compromise in the immune response.
Dr. Michael E. Pichichero
Innate immunity basically translates to the response of neutrophils, macrophages, and lymphocytes that are resident in the respiratory pathways or migrate there in response to signals from the site of infection that a problem is brewing. To start the process of innate immunity, chemicals are released from resident epithelial cells, lymphocytes, and neutrophils/macrophages. The chemicals are called cytokines and chemokines. The viruses enter the epithelial cells of the nasopharynx and tracheobronchial tree, and leave a change on the surface of the epithelial cells that alerts lymphocytes to kill and destroy those cells harboring virus. Neutrophils and macrophages ingest the bacteria by recognizing surface proteins on the bacteria that are foreign. Sometimes that is all that is needed, and the host clears the infection. But sometimes the innate response is not enough.
The innate response is good and bad. The bad part is that the release of the cytokines and chemokines and the migration of immune cells to the site of infection results in the release of even more cytokines and chemokines that cause increased inflammation. Microbes love inflammation. The inflammation caused by the virus, such as flu virus, creates a very favorable environment for the pneumococci. So the pneumococci start to reproduce in abundance. Then when the secretions of the nose are swept into the Eustachian tube and middle ear or the sinus drainage pathways and then to the sinuses or into the trachea and bronchi and then the lungs, we see the clinical manifestations of acute otitis media, sinusitis, or pneumonia. The innate response failed.
The adaptive response – as the word implies – is when the immune cells recognize and adapt to the presence of foreign microbes by recognizing their presence, migrating to lymph nodes and spleen, communicating with each other, and consequently multiplying into great numbers. The interaction between the immune cells – T cells and B cells – in the lymph node and migration back to the site of infection takes a few days to occur (3-5 days) if the host has prior immunity from prior infections or vaccination. If there is no prior immunity and no vaccination, then it takes 10-14 days for the adaptive immunity response to kick in and clear the infection. During that extra time, the pneumococci are gaining in numbers, causing more inflammation, and we see those clinical signs of fever, redness, and swelling at the site of infection, and pain.
So influenza can cause all of the events above by itself, but when the virus dances with the pneumococci, and the pneumococci benefit from the partnership, that is the most frequent cause of acute otitis media, sinusitis, and pneumonia. And all of that could have been prevented in most of our patients if they only got their annual flu vaccine.
Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. The study was supported by a National Institutes of Health grant. Dr. Pichichero said he had no relevant financial disclosures. Email him at pdnews@frontlinemedcom.com.