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New technology, better delivery of vaccines may reduce meningitis rates even further
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When was the last time you had a child with bacterial meningitis in your practice?
You probably can’t remember. Now there may be 24 cases of Hib meningitis in the United States annually.
Before Hib vaccine there were approximately 10,000 cases of meningitis caused by this organism. It was estimated that one in every 200 children would get invasive Hib disease, which in addition to meningitis, included pneumonia, orbital cellulitis, skeletal infections, febrile bacteremia, buccal cellulitis and others. These conditions too have largely disappeared. It is important that we maintain what has been accomplished.
Recently, there has been a problem with supply of Hib vaccine, which has resulted in a recommendation for a curtailed schedule. There have been scattered cases of invasive disease due to Hib reported.
In Minnesota in 2008 (MMWR. 2009/58/No. 3) there was a 17-year high of five cases of invasive disease, one fatal. These coincided with a fall both in the children receiving the required first-year doses and in children receiving the second-year booster dose. It was recommended that the latter be deferred in otherwise normal children in light of the shortage of Hib vaccine due to manufacturing difficulties. By parental choice, three of the cases were unimmunized. It was recognized early on that the disease incidence fell in unimmunized as well as immunized people, which has been attributed to herd immunity. It is likely that some of these five cases were a result of decreased protection of the unimmunized or partially immunized. In England, the initial recommendations did not call for a second-year booster dose. This did not have the desired result and the second-year booster was added.
Pneumococcal conjugate vaccine has produced a significant reduction in invasive disease due to this organism (NEJM. 2009; 360:244-256). The less than optimal coverage with this vaccine due to a variety of factors and the emergence of non-vaccine strains, particularly 19A, still leaves us some cases of invasive disease. A new 13-type conjugate vaccine, including 19A, has been submitted to FDA for approval.
The other member of the “big three” causes of meningitis has been meningococcus. Although most cases are sporadic, outbreaks on college campuses a few years ago focused attention on this organism and resulted in the recommendation for routine immunization of teens and selective immunization of college students. Unfortunately, getting vaccines into this age group has been no easy task. Fortunately, we now are experiencing a natural decline in meningococcal disease, which tends to be cyclic.
Although teens are the second most common group affected by this organism, the number of cases in the first two years of life far outnumbers those in the teens. Most of these have been Group B, for which there has been no successful vaccine. But help may be on the way.
The current vaccine contains groups A, C, W135 and Y, it does not contain Group B. Past efforts to produce such a vaccine have been frustrated by a number of factors. The conjugated capsular polysaccharide antigens for the four groups contained in the current vaccine produce good antibody responses. A similar preparation for Group B does not. Part of this may be due to the sequences this organism shares with human neural tissue. This may result in the host adumbrating the response to protect itself. Vaccine stimulated antibody against neural tissue also carries with it the possibility of autoimmune disease.
Another problem is that Group B seems to have several distinct subgroups so that a single vaccine may not protect against all strains. This may explain the localized success of Cuban and New Zealand vaccines against Group B.
Recently, there has been a new approach to producing a Group B vaccine. The organism has been sequenced and the results compared with the human genome to find sequences that are not shared. The sequences for surface antigens, which were very antigenic and in one case seemed to protect against a variety of strains, were expressed and the products combined to create a vaccine. The vaccine protected mice against a challenge dose of the organism. It now is in clinical trials. With a Group B vaccine and the existing vaccines it should be possible to achieve the goal of reducing or eliminating meningococcal meningitis.
The new technology for producing meningococcus B vaccine adds to our armamentarium. We still have neonatal meningitis, Lyme meningitis and tuberculous meningitis and a few others rare causes. If we can achieve better delivery of vaccines we already have or that are on the way, we may be able to refer to meningitis by the “big three” too as “rare causes.”