Monthly Archives: November, 2013

Meningitis Outbreak at Princeton University

I am a staunch proponent of vaccines and vaccinations, normally. When I learned of the meningitis outbreak at Princeton University I reacted positively to the report that they were offering vaccinations for an outbreak of meningitis. My graduate work involved the epidemiology and treatment of meningitis. Given my(admittedly dated)knowledge of meningitis the news details gave me cause for concern. So I took a long hard look at what is known about this outbreak and what are the plans. I begrudgingly have to say that I wouldn’t recommend this particular vaccination plan for the meningitis outbreak. In my opinion Princeton is trying to mollify students and possibly parents, not practicing good medicine. This plan may have a disastrous outcome for both the future of the vaccine, and the students of Princeton university.

I am not advocating in any way that approved vaccines are a problem, or useless. Vaccines are always a small risk and a large benefit. In my opinion, this plan fails to be effective with this vaccine because of incomplete data and the epidemiological specifics of this disease. The plan has the flavor of a feel good move, not a proper public health initiative. Realistically it will be offered to provide anxious students with a anxiety reducer. It will not be an effective epidemic treatment as outlined and it may actually have a negative effect on the situation. To explain I will have to do a short layman’s meningitis primer and a review of this situation’s specifics.

Meningitis is actually a description of disease not truly a single “Disease agent”. Meningitis is caused by many organisms. For this discussion I will use the term Meningitis to mean an infection of the meninges by the organism found in the Princeton University cases Neisseria meningitidis (meningococcus).

Meningitis is dangerous, it has a 10% mortality rate, and even among survivors there can be permanent disabilities. Brain damage, loss of limbs, kidney damage, major organ failure to name a few. Antibiotics can treat the infection but it is often not effective in preventing the complications. The organism infects a protected section of your body, and by the time you begin experiencing symptoms the disease is advanced. It progresses rapidly and can be fatal in as little as 24-72 hours from onset of first symptoms. The organism has an endotoxin that can be released on mass when antibiotics are introduced causing a cascading inflammatory reaction. The disease and what makes it lethal is actually far more complicated than I have the time to review here. It affects healthy and infirmed alike, yet the lethal illness is usually in the young and healthy. Meningococcus is spread through the exchange of saliva and other respiratory secretions during activities like coughing, sneezing, kissing, and in small children chewing on toys. It infects the host cell by sticking to it using Trimeric Autotransporter Adhesins (TAA). Though it initially produces general symptoms like fatigue, it can rapidly progress from fever, headache and neck stiffness to coma and death. There are different “Strains”, A, B, C, W135, X, and Y. All can be spread easily, yet A seems to be the most contagious. In the Princeton cases the B strain is involved. That is unusual in the U.S. B strain is commonly a European strain, A is in the middle east(so called meningitis belt). A, C strain predominates in US, with a disproportionate number of Y strain involved in college dormitory outbreaks.

There are currently three vaccines available in the U.S. to prevent meningococcal disease for people aged 2 or older. All three vaccines are effective against the same serogroups: A, C, Y, and W-135. Two different meningococcal conjugate vaccines (MCV4) are licensed for use in the U.S. The first conjugate vaccine was licensed in 2005, the second in 2010. Conjugate vaccines are the preferred vaccine for people 2 through 55 years of age. A meningococcal polysaccharide vaccine (MPSV4) has been available since the 1970s and is the only meningococcal vaccine licensed for people older than 55. MPSV4 may be used in people 2–55 years old if the MCV4 vaccines are not available or contraindicated. Information about who should receive the meningococcal vaccine is available from the Centers for Disease Control and Prevention (CDC). What is Glaringly missing from current vaccines in the U.S. is serotype B vaccine.

The school has decided to allow students to receive injections of a Novartis vaccine, which has been approved in the European Union and Australia but not by the U.S. Food and Drug Administration. It is specifically for Serotype B Meningitis. Novartis and FDA officials “have not yet come to an agreement on a pathway to licensure” for Bexsero, said Liz Power, a spokeswoman for the Swiss-based drugmaker. The U.S. Centers for Disease Control and Prevention received permission last week from the FDA to import the vaccine because of the New Jersey outbreak. Princeton will have the first of two doses of the vaccine ready in early December, with the second available in February; Two doses are needed for the greatest protection, the school said in a statement: “Students who already received a meningococcal vaccine are not currently protected against serogroup B, the bacteria causing the outbreak at Princeton.” The university said it will pay the costs of the vaccines for students who want to receive it.

Meningitis is a scary and contagious disease, so how could a vaccine be bad? Anti-Vax supporters have a dis-proven laundry list of why vaccines are terrible. Yet like a bad marksman they miss the target in this scenario. The Vaccine is not the problem, it is the administration.

In my opinion, the Novartis vaccine should be required for all students not currently immunized unless it is contraindicated due to a pre-existing condition. Failing that, voluntary immunization may not halt the disease and could have unintended negative consequences.

My opinion is based upon the limits of the vaccine, the complicated nature of the disease, and the unknown risks of the vaccine.

There is a reason that the vaccine for this strain has been difficult to design. Developing vaccines against Neisseria meningitidis serogroup B (MenB) has been a challenging aim for decades and was hindered by the close relationships between serogroup B capsule and the human antigen the neural-cell adhesion molecules (NCAM)2. The huge efforts made by the pharmaceutical industry in this field have led to a pioneer approach/concept called the reverse vaccinology that opened the way to develop not only a vaccine against MenB but also against many other diseases, that are otherwise difficult to be developed using conventional approaches. More than 15 years of intense research has led finally to the licensure of the Bexsero, the first vaccine against MenB. It should be undelined here the licensure of meningococcal vaccine is based on serum bactericidal assays and on the correlate of protection4,5 and no clinical efficacy studies have been required for the licensure of meningococcal vaccines. The Bexsero vaccine may offer a potential unique strategy against meningococcal disease (not only due to MenB) as the antigens targeted by the vaccine are conserved among meningococcal isolates regardless their serogroups.

Layperson summary: It is a novel approach that has a great deal of evidence supporting efficacy but it has not been thoroughly field tested. It was used with success to control a French outbreak last summer. It is not an experimental treatment but widespread use has not occurred even in Europe. You cannot experimentally infect people to test vaccines. All new vaccines are licensed and distributed based on laboratory testing. Additionally it is a two dose vaccine, meaning that it may be weeks to months for full immunization.

It is not just the “newness” or the schedule of the vaccine that is of concern. The nature of meningitis itself, overcomes the vaccine. Meningitis is spread through close human contact. In 9-20% of the human population, at anytime, meningitis can benignly colonize your Nares (Nasal Passages). Vaccines do not get rid of the colonization, it just prevents the internal infection. In meningitis there is no benefit of herd immunity. Meaning that in other communicable diseases like measles the un-immunized are protected when enough of the “herd” is immunized. The disease is stopped because it lacks the necessary carriers to keep spreading the infection. This is not the case with meningitis. Even the immunized can be carriers, infecting the unprotected.

In summary, immunizing a small voluntary population in this case has several major medical flaws.

The Vaccines primary efficacy in a large populations is untested.
The revolutionary nature of the vaccine makes the complications and risk/benefit profile a little more unpredictable than standard vaccines.
There is no Herd Immunity, so partially immunized groups will not make a major impact on halting an epidemic.
The complicated nature of sharing information about the vaccine’s limits may give newly immunized and un-immunized alike a false sense of security. This may result in a drop in traditional exposure precautions. More likely explaining the complicated issues to people will make them avoid the vaccine.
Bottom line: If Princeton is going to obtain FDA permission to import, buy, and administer this vaccine they better make sure everyone gets it, or it may fail spectacularly. Harming people and damaging the perceived public usefulness of the vaccine. You cannot undertake halfway measures with this disease and make it work. You must be “in for a penny in for a pound.”

For epidemic control this is shades of a placebo, to prevent a panic without substance. I am not recommending that your son/daughter at Princeton avoid the vaccine if it is available. What I am saying is that Princeton needs to go “all in” or kids will still get sick. Plus if your son/daughter is not immunized they may feel falsely secure about transmission. Worse current carriers may lose caution and continue to spread the disease. They hopefully will continue current practice of antibiotic prophylaxis in exposed adults. If they don’t it will be an even bigger failure.

Public health is not individual choice and privilege. Public health is using good science, and medicine to protect the public. Public health is what is good for the public not for the individual. A hard pill to swallow, but it only works if you really do what needs to be done. If you act like the “Wizard of Oz” all show and no substance you are really left with nothing worthwhile. This disease has the power to “pull back the curtain” and expose you as a charlatan.

Disclaimer: This post is my personal opinion, it does not reflect the opinion of: my practice, my partners, hospital affiliations, Brian Dunning or my academic affiliations. It is for informational/educational purposes only. It is not intended to replace personal medical evaluation and discussion with your healthcare provider.

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