Q&A with Head of CDC’s Meningitis and Vaccine Preventable Disease Branch Dr. Thomas Clark

Meningitis is an infection in the membrane layers surrounding the brain and the spinal cord called the meninges. It is airborne and is spread through close contact such as coughing or sneezing. The outbreak is related to type B (serogroup B) meningococcal bacteria which is the cause of the eight cases of meningitis at the University. The vaccine Bexsero has recently been developed and licensed in Europe and Australia to protect against type B (serogroup B) meningococcal disease. As has been announced by the Centers of Disease Control and Prevention (CDC) and Princeton University, the meningitis cases have been declared to be an outbreak. As a result, the CDC is importing Bexsero for use among students at Princeton University.

PPHR spoke with Dr. Thomas Clark, the head of CDC’s meningitis and vaccine preventable disease branch. Dr. Clark discussed the several considerations that went into the decision, the implementation strategies, the pros and cons of the vaccine and his thoughts on the concerns that have arisen due to the emergency importation of the vaccine.

PPHR: How did you come up with the decision to consider importation of the vaccine? What process did CDC go through while making the decision?

Dr. Clark: CDC is responsible for meningococcal vaccine recommendations and for surveillance of the disease in the US. We know the types of strains that cause the disease and how many people get sick, which are the basis of our vaccine recommendations. We have worked closely with the vaccine manufacturers and those who have developed the vaccine to understand how well it might perform in the US. We are quite comfortable with the vaccine under consideration for use at the University and its development process.

Several years ago, starting in 2008, there was a large outbreak on another college campus which ended up having 13 cases, including 1 death over a period of 2 years. The best way to control a meningococcal outbreak is vaccination, and at the time, we wish there had been a vaccine against type B meningococcal disease to recommend. We thought that at some point we would and it was due to the Novartis vaccine developed last year in Europe, which was a hurdle that needed to be crossed for us to even think about this in the 2008 outbreak.

As the outbreak was declared at Princeton University and the cases continued, we put the wheels in motion.

PPHR: There has been a recent publication that talks about the various considerations when implementing an immunization strategy. What considerations has CDC taken for the implementation strategy? Is there a post-implementation surveillance plan?

Dr. Clark: The decision to recommend vaccination is based on several factors including the timing of occurrence and the actual rate of the disease in the population. The goal is to know when the number and the occurrence of the cases suggest that there will be more cases. Certainly it was having a case occur after summer break that really made us concerned that more cases would happen.

Meningococcal disease is reportable in all 50 states and it is notified immediately to the state health departments because each case is considered to be a medical and public health emergency, in which there is a response that needs to happen. There is a requirement by the investigational new drug application for identifying and reporting any adverse events after vaccination. So disease surveillance will continue.

PPHR: How is it an outbreak? Is this rare for a college campus? Has a similar outbreak occurred elsewhere on a college campus in the past? If so, what control and prevention measures were implemented?

Dr. Clark: We typically define an outbreak as 3 cases at a university, college or other institution. When you have 2 cases, half of the time you don’t have any more cases. So it is really 3 cases that trigger the outbreak threshold that suggests that more cases will likely follow. And that’s when we start thinking about vaccination.

In the past, a lot of serogroup C outbreaks would occur on college campuses before the vaccination against serogroup C became routinely used in the US. Now, we rarely see a serogroup C outbreak One other thing is that serogroup C outbreaks tend to happen in a short period of time in which you have several cases within just a few days. In serogroup B outbreaks, you often can have weeks or even months in between cases. So it’s a lot harder to know when an outbreak is over without vaccination.

In 2008, there were about 4 clusters or outbreaks on college campuses of serogroup B meningococcal disease. And we know that meningococcal disease occurs in all age groups. However, adolescents and young adults are at a higher risk. College students living in dorms, especially college freshman, are at increased risk. They have always been the group which is considered to be at a higher risk, so the vaccinations and recommendations are for college students especially.

PPHR: Meningitis B is said to have several different strains. Has the strain at Princeton been identified? If so, how is the strain at Princeton different than the other ones? Is the vaccine meant for all strains of Meningitis B?

Dr. Clark: We basically classify meningococcal bacteria into serogroups which are A, B, C, Y, and W. And within the groups, you can do DNA fingerprinting to identify the individual strain. So in the Princeton outbreak, the strains from all the cases match one another. This strain has been seen before in the US although it is uncommon. It is known as ST409.

The different strains within serogroup N had been a key challenge in developing a universal serogroup B vaccine. There are some vaccines developed that are specific to a unique strain of serogroup B. The one that was used in New Zealand in a nationwide outbreak was a strain-specific vaccine, but it also is the basis for the vaccine that would be used at Princeton, which has other antigens which are common across the serogroup B bacteria. This makes it a universal group B vaccine.

PPHR: It is possible for students to be non-active carriers. Is there a way to know if someone is a non-active carrier?  What percentage of the students would you say are non-active carriers?

Dr. Clark: This is a kind of a tough concept. These are respiratory bacteria and so in a lot of healthy people, they will live in the nose and throat for some period of time and not cause disease, which is known as carriage. And in fact if someone is a carrier, (s)he usually develops protection that helps prevent the disease if exposed again.

It is really a few strains of meningococcal bacteria that are more likely to cause disease. If you acquire one of these virulent ones you either get the disease very quickly or you clear it. It can be cleared because your body develops an immune response and you get rid of the bacteria.

While it is possible, it’s not really feasible to test people to see if they are carriers. We don’t recommend doing that in order to figure out treatment and we don’t recommend treating people who are found to be carriers. It is not a matter of just one person carrying and continuing to transmit the bacteria. It is more of the fact that the transmission is sustained among the university population.

PPHR: What are the pros and cons of administering the vaccine on a college campus?

Dr. Clark: I think that vaccination is the best way to stop an outbreak. And it is the best way to protect people individually against meningococcal disease. But vaccination is voluntary so the students and parents will have to weigh the risks and the benefits of getting vaccinated.

The rate of the disease on the campus is quite high.

This vaccine like all other vaccines will have side effects, including pain, swelling or redness in your arm where the shot is given. Most of the time the side effects are mild or moderate and go away by themselves in a few days. There have not been any unusual occurrences of serious or permanent adverse effects of vaccination in any of the studies that have been done. But there is always a rare chance of a serious adverse effect. So students and parents will get information on that so that they can think the decision through with the facts at hand. And again it is possible that there could be additional cases and certainly we have seen it in the other outbreak we dealt with a few years ago.

Info to students and parents will be provided by the university.

PPHR: Why isn’t the vaccine approved by the FDA for the whole country?

Dr. Clark: The simple answer is that there has not been a finalized application made to the FDA to license the vaccine. There are studies that have been done on the vaccine and the results of the studies have been submitted to FDA but there is no final application that has been submitted. As a result they don’t have a complete set of information to base their decision on yet.

PPHR: What are your thoughts on the fact that the UK Joint Committee on Vaccination and Immunization’s recommendation to not distribute the vaccine because they think it will not be cost-effective?

Dr. Clark: I would say their concerns are of the cost effectiveness of such a program. This takes into consideration the occurrence, the rate of the disease and how much it would cost to vaccinate the entire population. In the UK, a program means that the government buys all the vaccines that are given to every kid in the country.

PPHR: What percentage of students do you estimate will take the vaccine? When would they given it out?

Dr. Clark: It is hard to say but the goal would be to provide everybody with the best information possible so that they can make a thoughtful decision and choose whether or not to be vaccinated. The goal would be to have as many people vaccinated as possible. But it is still an individual decision and is not a compulsory vaccination.

The time period is up to the university to plan, decide and notify the students.

[Princeton has notified the students that the first of two doses of the vaccine will be available in early December.]

PPHR: What are your thoughts from the epidemiologic perspective about students going home for Thanksgiving? Are there concerns about spreading the disease?

Dr. Clark: Meningococcal disease is pretty rare in the US and it continues to decline both because we vaccinate against some serogroups but also because serogroup B has declined for not completely clear reasons. Last year there were about 500 cases in the US among people of all ages. Everyday there are usually 1-2 cases, showing that there is a background rate of the disease. That being said, it would be very uncommon or unlikely for an outbreak to spread outside of the university. This is partly because the factors that promote transmission are really about the close interactions of students, their behaviors and their social interactions, which get interrupted when they are off the college campus and not interacting with the rest of the university population.

And if there is a case, people in close contact with the ill person are at very high risk to get the disease themselves and thus preventative antibiotics are given to them. This takes into account household transmission, including anybody who lives in the household with someone who gets the disease. But that’s why we remind people about the signs and symptoms of meningitis, and should anybody get sick, they should consult their doctor immediately.

However, you can’t really worry about somebody who may be a carrier and would spread it. There is nothing to do about that. I think folks should be reassured that it is unlikely that there would be any disease spread outside of the university during the break.

PPHR: Why are just students being vaccinated? What about the staff and faculty who might have kids and could act as carriers? Will the vaccine also be available to them?

The plan is going to be Princeton’s to announce. In general across outbreaks, the goal is to identify the population at risk and to vaccinate them. And it is rare to have disease in people over the age of 29 years. It is really the pattern of interactions among students that promotes transmission in most cases. In general, outbreaks in universities occur among the students rather than the staff and faculty.

[See announcement at http://web.princeton.edu/sites/emergency/meningitis.html that identifies populations at risk among the Princeton University community.]

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