Dr. Larry Pickering

Larry PICKERING:

TORGHELE: Today is February 2, 2017. I am Karen Torghele, and we are at the Centers for Disease Control and Prevention in Atlanta, Georgia, with Dr. Larry K. Pickering. In Dr. Pickering's career so far, he has been senior advisor to the director of the National Center for Immunization and Respiratory Diseases at the CDC [Centers for Disease Control and Prevention], executive secretary of the Advisory Committee for Immunization Practices, editor of five editions of the [American Academy of Pediatrics] Red Book, serves on the board of the Infectious Disease Society of America, and is currently adjunct professor of pediatrics at Emory University School of Medicine. Welcome, Dr. Pickering and thank you for agreeing to be here for the interview for the Global Health Chronicles Oral History of Polio Project.

PICKERING: Thank you.

TORGHELE: To begin with, would you just tell us a little bit about how you came to be in medicine and public health specifically, and just a little bit about your background?

PICKERING: I think it's interesting to go over why I went into medicine. I think 00:01:00it was because of an illness that my mother had when I was very young. I always knew I wanted to go into medicine just because of that. I saw the suffering she went through. When I went to medical school at West Virginia [Univeristy] and then I did my training in St. Louis at Washington University, it became evident to me that taking care of patients was wonderful. Sick patients were great to make better, but after doing that for a few years, I realized that maybe there's a way to prevent people from getting sick and have a broader impact on the health care system. Then I became interested in various aspects of public health and preventive medicine.

TORGHELE: After you went to medical school, what did you do?

PICKERING: Well, after medical school, then I did my internship residency and fellowship at Washington University. Following that, my first academic appointment was at the University of Texas Medical School in Houston, where I 00:02:00was an assistant professor of pediatrics. Luckily, during my time there I became involved with the American Academy of Pediatrics. I was put on their committee on infectious diseases, which is a committee that the AAP [American Academy of Pediatrics] has that deals with all infectious disease and vaccine-related issues. They make recommendations for the American Board of Pediatrics.

TORGHELE: Would you tell what you specialized in, and what your fellowship was in?

PICKERING: My fellowship was in infectious diseases. It was a fellowship that was done at Washington University with Dr. Ralph Feigen, a wonderful infectious disease physician. I really became motivated to take care of sick patients during my fellowship. And then during my first academic appointment at the University of Texas Medical School in Houston, as a young assistant professor, I began to realize that taking care of sick patients was very rewarding, but there was another thing that could be done, and maybe that was to prevent illnesses and diseases and accidents in individuals. That's when I became interested in public health, particularly in the immunization aspect of public health. That was further stimulated when I was appointed to the Committee on Infectious Diseases--COID--of the American Academy of Pediatrics. Now that's a committee 00:03:00that makes all of the vaccine recommendations and handles all the infectious diseases for the American Academy of Pediatrics. That was where I became further interested in the issues of immunization.

TORGHELE: You went from being at University of Texas to going, next, to where? Where did you go from there?

PICKERING: After that I went to Virginia--to Norfolk, Virginia--and ran the Center for Pediatric Research there for several years. After doing that for four or five years, I realized that I really was interested in public health, and had the opportunity to meet with Dr. [Walter A.] Walt Orenstein, who was the head of the National Immunization Program at the CDC. Luckily for me, he offered me a position to spend a year with him at the NIP [National Immunization Program] working on various vaccine issues, which I accepted immediately. My wife and I 00:04:00moved to Atlanta, Georgia, to spend a year. Well, that year turned into fifteen years. After working with Walt for four or five years at CDC, I was then asked to become executive secretary of the ACIP [Advisory Committee on Immunization Practices], which I thought about for a long time and then readily accepted. It was a very important position, and I was honored to have been offered it.

TORGHELE: Did you know anything about the Centers for Disease Control before you came to work there?

PICKERING: I knew a little bit about CDC. As a faculty member at the University of Texas, I was interested in diarrheal diseases and infections in childcare centers, and CDC had several very capable people in both of those areas. Through a grant from CDC and through working with the laboratories and the experts in various diarrheal diseases at CDC, I became fairly knowledgeable of some of the activities. I say "fairly knowledgeable of some," because there's so much that goes on at CDC, it's impossible to really encompass everything that happens. But 00:05:00I did appreciate everything that happens, and the people that were there at that time that I worked with.

TORGHELE: Did you have exposure to any of the publications that came out of CDC before you came to work there, and can you describe that?

PICKERING: That's an interesting question because the one publication that comes out of CDC, of course, is the MMWR, Morbidity and Mortality Weekly Report, and I had little knowledge or concept of what that was until I came to CDC. It's an absolutely wonderful publication that now I, of course, read from cover to cover whenever it comes out, but I didn't have the knowledge of that before I went there. Now, whenever I give a lecture or wherever I give a talk, I always highlight that publication that people can get free of charge. It's wonderful. I was also aware, of course, [of] other publications that individuals from CDC published, originally in diarrheal disease, and then as I became more immersed 00:06:00in vaccine-preventable diseases, the many publications that came from CDC on vaccine-preventable diseases, and things that came from ACIP before I was fully involved in the ACIP.

One other thing that I began recently, within the last few years, is to write a synopsis or a summary of various articles that are published in MMWR, and then that summary or synopsis is published in AAP News, which is a monthly publication that all pediatricians throughout the country receive. Recently, I've involved our pediatric fellows at Emory in writing these articles, which is wonderful for them, wonderful for me to see them develop their writing skills, and also I think very useful to pediatricians in practice because these are practical articles that will help them in their practice of medicine and taking care of children.

TORGHELE: And must save them time, too.

PICKERING: Yes, it does, and most pediatricians aren't aware of the MMWR, and this is another way that we can get pediatricians in practice to sign up for MMWR, get it electronically. There is always something in each issue of the weekly MMWR that is useful for patient care.

TORGHELE: So now we're up to when you started your work at the Centers for Disease Control, and what year was that? And describe how it was when you first came, if you don't mind.

PICKERING: I started at the CDC in 2001, somewhere around there, working with Dr. Orenstein, who is wonderful. The opportunity to really help him with some of the vaccine issues--with some of the vaccine adverse events that vaccines were accused of causing, but really didn't--and just to work on many of the issues that the old National Immunization Program dealt with, like vaccine supply, 00:08:00vaccine distribution, mistakes people made when they give vaccines--the whole myriad of problems and issues that most people don't realize happen, that are handled very smoothly, were handled very smoothly, by the National Immunization Program.

TORGHELE: So it sounds like a lot to take on. Could you take an example of something that you might do with a typical issue?

PICKERING: One example that I worked on--as well as many, many other people--was when the rotavirus vaccine--rotavirus, of course, causes diarrheal disease, and there was a good vaccine that prevented this disease in infants. It was given to infants at a very young age. Well, because of the systems that are set up at CDC to monitor potential adverse events of vaccines--the vaccine adverse events reporting system [VAERS] is one--there was an indication that there was 00:09:00something called intussusception, which is a bowel blockage that was occurring in infants, some infants, very rarely after they received the rotavirus vaccine. Well, the monitoring system which we have picked this up, and the individuals who work with rotavirus were told about this. And they did a thorough investigation and found, yes, it was associated--very, very rarely, but it was recommended that the vaccine be halted because of this very rare adverse event, despite the fact that this vaccine saves lives--not only in this country, but worldwide--from severe diarrheal disease.

So the investigation definitely proved there was an association. But, luckily, two other vaccine manufacturers persisted in making different rotavirus vaccines that eventually went through the studies to get them approved, went through ACIP to make recommendations that it be used routinely. And now we have a very 00:10:00vigorous, strong, trustworthy rotavirus vaccine, given to infants to prevent diarrheal disease and prevent deaths that occur. It's remarkable. We don't see much rotavirus disease now in infants that are immunized. It is two very good vaccines that further strengthen our immunization program for children.

TORGHELE: When you first get the reports, how does that happen? Do your private physicians call in to somewhere and then the health department calls CDC? Tell me how that works.

PICKERING: The Vaccine Adverse Events Reporting System is a system that is mandatory reporting of an adverse event by physicians, laboratories, and so on. These are reported to VAERS, as it's called. Then there are people who monitor VAERS regularly, almost every day, for reports that come in. With rotavirus, for instance, they noticed that, Wait a minute, there was a little bit of an uptake here in this intussusception. So when they noticed, number one, an uptake of 00:11:00something; when there is a death associated with a vaccine, whether or not it's due to it; or when there is a severe adverse event; then those are further investigated to see whether or not there is any association with the vaccines. For most of them, there is no association. But it's very heartwarming to me and to many of us in the field that we have these systems that monitor vaccines and pick up adverse events, which are, of course, very rare in vaccines in our immunization program.

TORGHELE: Sounds like an incredible system.

PICKERING: It is really incredible. And that's the first step, and then if there is an indication, then there are further mechanisms that are used to prove whether or not it is associated. So the whole system of reporting and follow-up and really delineating whether these vaccines cause adverse events is a very sound, solid, and proven system.

TORGHELE: Once you find that there may be an association with an adverse event 00:12:00in a vaccine, what are the steps you take then to convey that information?

PICKERING: Well, first of all, it depends on how bad the adverse events are. It's interesting because a lot of the adverse events that are reported that you hear from people in the community, or you hear this vaccine causes autism, have no proof. Most of them are background events that would have occurred whether someone got the vaccine or not, and there's really no association. But if there is one, then the folks at CDC, working with their partner organizations, will determine what is the best route to follow with regard to continuing that vaccine if it's a minor adverse event, or taking further steps to investigate or to stop using it.

For instance, we know very well that the HPV [human papillomavirus] vaccine is a very safe vaccine, but it is associated with pain during injection. That's been picked up in the clinical studies that were done before it was licensed and given. We know that occurs. It's something that's told to people before they get 00:13:00the vaccine--they know about it. And it's an adverse event that does occur, but it's basically about the only adverse event with the HPV vaccine, which prevent cancers in women and men, that we see.

TORGHELE: So even though it's not a serious adverse event, if the people are prepared, you want them to know that there is something that's associated with the vaccine.

PICKERING: Absolutely. There's nothing that's hidden. If we find something that is associated, then it generally will be added to the consent forms that people get, and it will be explained to them. The point to remember is that the studies that are done in the thousands and thousands of people that receive the vaccine before the FDA [U.S. Food and Drug Administration] licenses it will pick up most of these common adverse events. We know what they are. Most of them are pain at the injection site, and soreness and swelling at the injection site. That's the major thing that you see. The real serious ones, of course, require hundreds of 00:14:00thousands of people to be immunized, and we have the systems to really monitor whether there are any serious adverse events following vaccines in these larger populations.

TORGHELE: So you brought up another organization that you might work with when vaccines are coming out. Would you mention some of the other organizations that work with CDC, and what their roles are?

PICKERING: I'll use the ACIP as an example. The ACIP is a federal advisory committee; it's been chartered. It makes vaccine recommendations for the civilian population and the military population in the United States. It reports to the CDC director and the secretary of HHS [U.S. Department of Health and Human Services], who sign off on the recommendations, and then they're implemented. Now, the ACIP is interesting. There are fifteen voting members on the ACIP--fifteen--and they come from a very wide background of expertise. Then, at each of the ACIP meetings, there are about thirty liaison organizations. 00:15:00These are organizations that deal mostly with implementing pediatric or adult vaccines or providing education about them. For instance, of the liaison organizations, the American Academy of Pediatrics, the American Academy of Family Physicians, American College of Physicians, nursing organizations, they're all there at the meetings to give input to the ACIP members when appropriate. It's a very good system.

TORGHELE: You would be uniquely qualified to talk about the ACIP because you wrote the article with [Dr.] Jean Clare Smith and [Dr.] Alan Hinman in the MMWR article "History and Evolution of the Advisory Committee on Immunization Practices, 1964 to 2014." What can you tell us about the history of ACIP, how it came to be, and the role it has in polio and other immunizations?

PICKERING: The ACIP's first meeting was in May of 1964, and met regularly. Each of the years that the ACIP has been in existence, it's been fine-tuned and improved. In 1972, the ACIP was designated as a federal advisory committee that reports, as I said, to the CDC directly. The ACIP will consider vaccines after they are licensed by the FDA and then make recommendations for use of those vaccines in pediatrics and adult populations.

The ACIP meetings, interestingly enough, are all open public meetings, so anyone can attend. You can watch the ACIP meetings on your computer screen. They're all telecast, three times a year, here in Atlanta at the CDC. They're open to the public. Public comments are taken, and this is very important. There are public 00:17:00comments taken before the ACIP makes a vote, and that gives the ACIP members an appreciation of what public participants feel. Many of the public comments we get when a vote is taken deal with disease that will be presented by that vaccine. Let me give you an example. We had a recent vote on meningococcal B vaccine, and the group of parents who had had children die from that organism, meningococcal B, were there at every meeting that this vaccine was discussed. At every public meeting, they gave their opinion that this should be a vaccine that should be given to all adolescents to prevent deaths in other adolescents so that they did not need to suffer. It was very moving, very important, and very appreciated by the ACIP.

TORGHELE: Were there people who also presented the other side of that?

PICKERING: Initially, when I first started with ACIP, there were a lot of people who were so-called anti-vaccine and would really express their opinion about 00:18:00potential adverse events with vaccines. Since many of these theories have been debunked now with science, we don't see many people who are anti-vaccine people. There will be individuals that come and say, Well, you need to be careful of this vaccine because it might do this or might do that, and they're listened to. They are listened to by the committee members. Their comments are always made, as I said, before a vote is taken, so that ACIP can consider them. Most of the comments now we hear are from parents who support the specific vaccine that's going to be voted upon because they've seen those diseases in their relatives, children, wives, husbands, and so on.

TORGHELE: Tell us about a time when the committee had to make a decision that specific--maybe that stands out in your mind--how the decision was made, what 00:19:00you base your decision on, what sources of information, and how that all comes into play with your decision.

PICKERING: The decision process from ACIP is fairly complicated. ACIP has fifteen members. They are the only ones that vote. They are thirty liaison organizations. They don't vote, but they participate in the meetings and let the ACIP know what their organization wants. For instance, if there's a vaccine being considered for a pediatric patient, the representatives from the American Academy of Pediatrics will express how the AAP feels about this and what the Red Book committee that we talked about is doing. That's one aspect of it. The second aspect is that we also have at the meeting the public, and we also have members from FDA, NIH [National Institutes of Health], and so on that are there 00:20:00to answer questions that the ACIP may have about a specific vaccine.

So when does the ACIP consider a vaccine? Generally, the consideration occurs after FDA has licensed a vaccine. FDA licenses vaccines for use in the population in the United States. So once a vaccine is licensed, then the ACIP considers the recommendations. The FDA licenses--they don't make recommendations for vaccines. They license it under certain conditions. The ACIP then looks at the vaccine, looks at those conditions, and generally will make a recommendation similar to what the FDA has licensed the vaccine for. Sometimes they're a little bit off label, but that's how it's done.

Now, what does FDA consider? Well, the FDA considers a vaccine once a biological license application, a BLA, is filed with them by a vaccine manufacturer. Vaccine manufacturer spends years doing vaccine development, clinical studies to 00:21:00prove that it's effective, safe, and that they can produce the vaccine, and then the FDA considers it. The FDA then does one of three things. One is it gives it an approval; two, it gives it an accelerated approval; or three, it denies approval.

So, say it gets a traditional approval. That means that the vaccine can be given to all people in a certain group, a certain age group, or those with an underlying disease or condition. The accelerated approval means that the FDA still needs a little more data on various aspects of this vaccine, but because this vaccine will save lives immediately or prevent serious disease, then they get an accelerated approval. Now, that accelerated approval is contingent upon the vaccine manufacturer gathering additional data to present to them, and then once those data are gathered, then the FDA will give a traditional approval or 00:22:00take the license for that vaccine away. Meningococcal B vaccine is a good example of traditional. This is a vaccine that more data are needed, but it saves lives from a very lethal, terrible disease, so that was given an accelerated approval.

Then the ACIP gets the FDA approval, and then they discuss it. Before the approval of that vaccine, they will have been discussing that vaccine, because they know what has been submitted. So there is a lot of data that are presented--not only what FDA presents, but there are other studies that the vaccine manufacturer may not have presented to the FDA that the CDC or the ACIP considers in making their recommendation. Usually, the recommendations from CDC follow the licensure of the FDA, but sometimes they're a little bit different. But basically most of the times they're similar.

TORGHELE: That's a very good explanation.

PICKERING: It's a really complicated process. It's hard to understand, but it's a lot of time, trouble, and work that people put into the whole vaccine process to get a final product that saves lives. It's an amazing process.

TORGHELE: Can you describe a vaccine trial, how that works? Who does it? Who participates?

PICKERING: The vaccine trials are conducted by the vaccine manufacturers, and they will contact people, for instance, in academic medicine, and they will enroll patients into a vaccine trial. So, say you have Vaccine A. They have people that will get Vaccine A and people that may not get Vaccine A, and then they follow those people to see whether or not vaccine prevents the disease. They also are following them very closely for any potential adverse event, to make sure that the vaccines are perfectly safe. So safety and efficacy and 00:24:00immunogenicity and effectiveness are all things that are looked at.

It's pretty standard, what the FDA requires. It's pretty standard for a vaccine manufacturer in the biological license application to be told what to do. They know what to do. This has been done over and over and over for vaccines. Then the data are all analyzed, and they are presented to an advisory committee to the FDA. If the advisory committee of outside experts says, Okay, this looks like a pretty good vaccine, we think you should consider it, then the FDA will consider it. The consideration by the FDA is very, very extensive. Once they agree that, Yeah, this looks like a vaccine, it's safe, effective, we will license this vaccine, then it's licensed, and then the ACIP process kicks in.

TORGHELE: In situations where other countries may have had the vaccine first and done vaccine trials, do you ever consider that data as well?

PICKERING: Those data are considered once in a while. I'll give you an example. One of the things that the ACIP noted with pertussis, or whooping cough, is that the vaccine--the acellular vaccine, which is the newer type of vaccine--may not be quite as effective as the old vaccine. It was changed. We can go into that. So what the ACIP did is said, Okay, let's look at the people who are dying from pertussis to really put an emphasis, because we want to save lives. Lo and behold, the major group that was dying from pertussis was infants. That's the group that dies. Terrible, terrible disease in an infant. They were the ones that were dying. So the ACIP said, Okay, how can we prevent this disease in infants? They said, Okay, we can immunize them. Well, immunizing infants beginning at two months of age, four months, and six months--six months is when they die, and you can't get enough antibodies into them to really protect them. 00:26:00So they said, Okay, what else can we do? Ah, we can immunize mothers when they're pregnant. Whoa.

Well, everybody said you don't give immunizations to pregnant women because they might cause side effects. That's what we've all discussed and learned and know about. So what happened was, at the meeting where this was being discussed by the ACIP, is whether to implement a vaccine program in pregnant women to prevent death in infants. There were two people there. One was [Dr.] David Salisbury from the United Kingdom, and he came up to the microphone and he said, We've been doing this for over a year, and we have a perfectly good safety record. All the community members said, Wow, we feel better. Then there was another gentleman there from, I think, Australia, who got up and said the same thing. He said, We've been immunizing pregnant women, and our safety track record is really pretty good. So the ACIP members felt much better. I know I felt much 00:27:00better. I wasn't a member, but I felt much better that we have people from other countries that have done this already and the safety record is good. Because that's the critical thing, the safety record.

So the ACIP decided to recommend that this vaccine be given to pregnant women, usually in the middle--beginning to the end of the third trimester. That allows the mothers to build antibodies. The antibodies pass into the infant and they're protected against pertussis. The ACIP said, Wait a minute, okay, we're going to recommend this, but we still want to know about safety. We want to report on the safety of this vaccine given to women in the United States at every meeting. So at every meeting there have been safety reports that have been given. There have been no side effects whatsoever. It's been wonderful, because not only did they just watch women, but they set up really complicated studies to monitor mothers and to monitor infants to make sure there was no side effects. Guess what 00:28:00happened? Pertussis in the infants has gone down, perfectly safe. They saved lives by this. And this shows how the cooperation with an international community, what they have been doing that we weren't--provided those data.

TORGHELE: That's a great way to maximize that information, too.

PICKERING: Absolutely. It shows how we need to interact in many areas--but in the vaccine area--with our colleagues in other countries. And we also have many examples how ACIP and CDC work with members of other countries, particularly in setting up ACIPs in other countries. It's a great system.

TORGHELE: It just sounds like a great system. Dr. Pickering, would you tell us about oral polio vaccine versus the inactivated polio vaccine, and how decisions are made about which to use when, and where? Because I know that several changes have been made over the years since it came to being.

PICKERING: First is the OPV [oral polio vaccine] era, the oral polio vaccine 00:29:00era, which was 1961 to, I believe, around 1997. Then from 1997 to 2000 was the second era, and that was the sequential era, where inactivated polio vaccine was utilized with the oral polio vaccine. Thirdly is the IPV [inactivated polio vaccine] era, where in the United States only inactivated polio vaccine was utilized, and that began in around 2000. The ACIP, of course, made recommendations in each of these cases, but also the American Academy of Pediatrics made recommendations in each of these cases, and they weren't necessarily always the same, because of different considerations that they had. They considered the same data, but sometimes looked at it a little bit differently.

TORGHELE: There are some lively discussions, I imagine, from people with 00:30:00differing points of view. How does that work when there are discussions like that?

PICKERING: There are lively discussions. In fact, there are oftentimes lively discussions about every vaccine, and it shows that people are using their background data and knowledge to really express how they feel. There were discussions at the ACIP before the vote was taken--I think in June of 1996 for the ACIP--for the sequential schedule. People looked at the data differently. One of the problems with the oral polio vaccine, which was very uncommon, was called VAPP--vaccine-associated paralytic polio, where somebody who got the oral polio vaccine, [who] may have an underlying immune condition, would develop polio from the vaccine--very, very rare. Secondly, since this was a live viral vaccine, it is excreted in stools, so somebody who was exposed to those stools could catch the virus and get vaccine-associated paralytic polio. It was very 00:31:00uncommon, one in a million or whatever--that's not the exact figure, but it was very, very rare.

So when people considered these two vaccines--when the inactivated polio and the oral polio were considered, which should be given--they consider things like safety. They consider things like efficacy. They consider things like, How do these vaccines--how are they going to fit into an already complicated immunization schedule? How are we going to explain these schedules to pediatricians who are already busy with many other things, including many vaccines? All of those things are considered, and as you can imagine, each person would consider one thing differently than the other. I may think that VAPP, vaccine-associated paralytic polio, is a number one consideration. Somebody else may think, No, they're both pretty safe vaccines. How is it going to fit into the schedule? That's my major consideration. So those are the things that were considered.

There was a lot of lively discussions, because people would feel that you could do three things--three ways to give these vaccines that began around 1997. Number one is you could give a sequential schedule, two IPVs and then two oral polios. This adds four vaccines into the schedule, but it basically is a major way to prevent the VAPP, the vaccine-associated paralytic polio. Number two is you give all oral polio, or number three, you give all inactivated polio vaccine. It's interesting because when the ACIP voted, they voted for sequential schedule--two IPVs and then two oral polios. The AAP committee had very contentious discussions because they had different opinions, and each of the members had their opinion, and there were people that supported all three. The Board of Directors considered the COID [Committee on Infectious Diseases] 00:33:00recommendations, and they decided to leave it open to a decision a physician would want to make. So the physician may give all IPV, he or she may give all oral polio, or he or she may give sequential schedule.

So there was a little bit of a difference there between ACIP and the American Academy of Pediatrics, although the differences were not in the quality of the recommendations, just how the vaccines were given. Well, that all got squared away around 2000 when the 2000 Red Book came out. The recommendations were pretty much harmonized, and then in 2000, of course, the recommendations were made to give only the inactivated polio vaccine, which is what we do now. It was interesting to hear the discussions, because there were a lot of very bright people pleading for the way they wanted to have it done, and very respectful, intellectual discussions were held about an extremely important topic. Nobody 00:34:00disagreed that polio was a terrible disease and that we should eradicate it from the United States. Everyone agreed with that. It's just that how we got there was a little bumpy for a few years. But things have now straightened out.

TORGHELE: It sounds like there were some practical considerations there that the pediatricians had.

PICKERING: Yes, the pediatricians did. You have to look at the pediatrician who runs an office. It's very busy, there's a lot of vaccines. Polio isn't the only one. What's the easiest way to maximize protection and coverage? That was, of course, one of the major considerations, knowing that they were all good. One wasn't better than the other. It's the implementation issues and the safety issues that were the major considerations.

TORGHELE: Did you ever have people who had gotten the disease from the vaccine--someone with VAPP, for instance--come to a meeting? What effect did that have on people?

PICKERING: There were people that were at one or two of the ACIP meetings that I 00:35:00remember that were in wheelchairs that had had polio, and, of course, when you get it, sometimes you have lifelong problems. I think that having somebody there in a wheelchair--there were several in the meetings, and seeing that is very powerful, very powerful, with regard to making sure that everybody gets this vaccine--and in some people's minds, making sure it's IPV first and then OPV, or all IPV, to prevent any vaccine-associated paralytic polio. But yes, there were some people that came that actually had the polio disease and that was very, very moving.

The other thing is I remember somebody--when we did our diarrhea studies in Mexico, one of the people who worked in a microbiology laboratory there over the 00:36:00ten or fifteen years that I got to know her, she had had polio, and she developed a limp, and then she was walking with crutches, and then she was wheelchair-bound. So I saw this process of how ravaging polio can be on a person--this wonderful lady in pain and with disability. And it's so wonderful now that we have polio eliminated from this country and are working very hard to have it eliminated worldwide. That will be a major, major accomplishment. Thousands and millions of people's lives will be saved, and lives that would have been significantly altered by having this disease--we won't see that anymore. It's going to be a really neat time.

TORGHELE: Talk to us a little bit about the Red Book, if you would, because you edited that five times.

PICKERING: Yes, five editions, fifteen years. Yes. The Red Book is the 00:37:00publication from the American Academy of Pediatrics. It comes out every three years. It covers all of the infectious disease issues as well as vaccine issues and a lot of other things that deal with the field of infectious diseases. I was editor after George Peter became editor. He was editor before me--wonderful person, set up a real legacy with the Red Book. It's written by people on the committee on infectious diseases, but the interesting thing is about the Red Book is that the chapters are all reviewed by CDC. Each chapter is reviewed by at least one CDC person, and there are like three hundred and something chapters in the book. It's a huge undertaking. Secondly, various other chapters are reviewed by people at NIH, FDA, and then the experts throughout the world. So if you talk about something like pertussis, we know the experts throughout the 00:38:00world will review the chapter, so it's wonderful.

The other thing about how wonderful CDC people are is that when I was editor of the Red Book during all the times, there were about 350 CDC people who would review various parts of the Red Book. Nobody from CDC ever declined reviewing one of the chapters in the Red Book, which was, to me, phenomenal, because people are very busy and we all get requests to do things. Of course, they got a free book when they did it--that was part of it, but I don't think that's why they did it. That really added an expertise to the Red Book, and it also made sure that recommendations from CDC and the American Academy of Pediatrics were on the same page, so to speak. They are in agreement because we don't want to have differences. That really confuses people.

I was really very honored to work on the Red Book during this period of time. And a lot of transitions occurred, as they do in the field of medicine, and it 00:39:00has come a long way. The other interesting thing is that the first Red Book was published in 1918. That was the first one. There were eighteen diseases in that Red Book; it was nine pages. Now the Red Book is a thousand pages and there are hundreds of diseases in it. Of those eighteen diseases that were first published in the Red Book, I think eleven of them are now vaccine-preventable. The other ones, of course, are more symptomatology diseases, like strep throat and so on. So eleven of the eighteen now we can prevent. But it shows the huge amount we've learned in the field of medicine since 1918, and yearly, the advances are just phenomenal.

TORGHELE: Why is it called the Red Book?

PICKERING: That's a good question. It's called the Red Book because it has a red cover. This was started a long time ago. This was the original Red Book, 1918. See how thin that is? This is the one I have from 2000, when some of those polio recommendations were made, and it's a lot thicker. The red cover on the Red Book 00:40:00was why it was called the Red Book. During the time that I was on the committee, there were people that said, Well, maybe we should change the color of the Red Book, and of course that went over like a lead balloon. And it's always stayed that color, and that's just what it's been called. It's really the Committee on Infectious Diseases textbook on infections and vaccines.

Lastly, the Red Book, of course, is approved by the board of directors of the American Academy of Pediatrics. They have reviewers themselves. There are three reviewers from the board that review all the Red Book to approve it. So it undergoes a very extensive review. A couple years ago we started having online pictures, so that if you wanted to see somebody that has a strep throat or some other abscess or infectious disease, you can go online and there will be pictures with each of the chapters--illustrations with each of the chapters you can learn, because it's a learning tool also.

TORGHELE: I imagine that's pretty important for physicians who were trained 00:41:00later and never saw a case of polio, for instance.

PICKERING: Yes, it is, and that's the interesting thing. A lot of younger physicians have never seen these diseases. They give the vaccines and just move on, but they don't fully appreciate Haemophilus influenzae. When I was a fellow in St. Louis, we always had four or five children with Haemophilus influenzae meningitis in the hospital. Many of them would be brain-damaged. Many of them couldn't hear when they completed their course of antibiotics. Now, we don't see that disease. We see it, but it's very, very rare because of the Haemophilus influenzae vaccine.

TORGHELE: You wrote an article, too, with [L.] Reed Walton and Walt Orenstein, "Lessons Learned from Making and Implementing Vaccine Recommendations in the U.S." That was published in the American Journal of Preventive Medicine. Can you tell us about that article?

PICKERING: Yes, it's interesting. When ACIP makes vaccine recommendations, the committee members think and try to cover all aspects. We want to make sure we've covered everything about this vaccine, so that when it is licensed and used, there are no surprises. Well, there are surprises. There are lessons learned. So we had in that article seven or eight lessons learned, and I'll give you one positive and one negative. We'll start with a negative and end positively. The negative one was, a while back, wholesale pertussis vaccine was thought to be associated with encephalopathy. Since, it's been proven that wasn't the cause of the encephalopathy--it was something else; it was a genetic condition. So because of these bad fevers and irritability and encephalopathy that the wholesale vaccine caused--they did cause those adverse events, but they prevented pertussis--because of those adverse events, the manufacturers developed and marketed and licensed an acellular vaccine. The acellular vaccine 00:43:00was going to have a lot less side effects and therefore protect kids against pertussis, but none of these side effects.

The good news is that the side effects were a lot less. The bad news was that the immunogenicity, or the protective titers, aren't nearly as good, long-term-wise, as the wholesale vaccine. So we made a change to better side effects, to decrease them, but we also negatively impacted the protective effects of that vaccine.

Now with the positive. The positive was that pneumococcal vaccine--pneumococcus is a bacteria. It causes meningitis, arthritis, bacteremia, really bad infections. It's one of the major causes in the elderly of death. When the elderly go into the hospital with pneumonia, they often have either flu or pneumococcal pneumonia or both. This was a disease we wanted to prevent. So 00:44:00there were a couple of vaccines that came out; pneumococcal-7, which was seven of the antigens and then thirteen antigens. This vaccine was wonderful. The disease rates just dropped in pediatric patients. It was unbelievable. But what else did we notice? We noticed that not only did the disease decrease in the immunized children, we saw a marked decrease in invasive disease in adults, in the elderly adults. Why would a vaccine we give to children decrease the infection in adults?

It's called herd protection, herd immunity. We call it community immunity, because what happened was these little critters called children would become colonized with strep pneumonia, they'd be around their grandparents or parents, and they would give these organisms to their parents or grandparents. Now, if a grandparent had not been exposed to pneumococcal-19, which is one of the many 00:45:00serotypes, then he or she would have a good chance of that organism getting in the throat, disseminating throughout the body, and causing very severe disease. This is an example of a completely unexpected positive effect of a vaccine, when the ACIP made that recommendation. Giving it to a kid protects the kid, but because the organisms are not excreted through the nasopharynx, it also protects the elderly adults. Phenomenal, absolutely phenomenal. No idea that that was going to happen, but that was one of the very positive benefits. So we illustrated some of these things in six or seven of the areas where we wouldn't have expected something like this to have happened, but it did.

TORGHELE: So you've included things like that in your report as well.

PICKERING: Yes. I think it's important when vaccines do come out and are used in millions of people, compared to thousands that are studied, there are very good surveillance systems set up to see how they work. The pertussis one we saw 00:46:00doesn't work quite as well. The pneumococcal protects extra people, the elderly. So we want data on how they're working to make sure that we're not missing anything.

TORGHELE: How did you determine that the pneumococcal vaccine was protecting [the] elderly? How did that manifest itself?

PICKERING: That's a good question. I think they began seeing decreases in the illness in the adult populations. There was a big study going on using this vaccine in adults to prevent the infections in adults. I think they started seeing, maybe, the rates of background natural disease go down because they had rolled patients and controls in that study. They started seeing the background rates go down there, and that may be one. Also, maybe throughout the country we began seeing, Hey--and the reports of these conditions, because these often times are reportable--we saw a decrease of invasive pneumococcal disease in the elderly, and then started looking at the different serotypes, and the vaccine 00:47:00and the serotypes that were causing disease and not causing disease, and some smart person made the link. That's why we have the follow-up systems, exactly for this reason.

That's what CDC's so good at. One of the things CDC's so good at is really the public health aspects of setting up these studies and monitoring them so that data are continually acquired after a vaccine is licensed. We don't stop acquiring data. We continue to gather it for further improvements and just to show that these vaccines indeed are working well.

TORGHELE: How has the anti-vaccinators movement impacted immunization work?

PICKERING: I think it has impacted. I think it's impacted it negatively, because of the feelings that people have about vaccines and the stories they tell. There's not a lot of science to support many of these associations. We have 00:48:00VAERS set up to detect associations with vaccines that are available. I think that why people make these judgments and why they are so anti-vaccine is disturbing. Oftentimes, the things that they say and do are not based on science, and oftentimes people won't listen to science. You find people gather together in little communities that all have these same beliefs. And it is unfortunate, because not vaccinating children really causes a major problem, not only in death and disability, but the social cost of dealing with all of these episodes that we don't need to deal with are unfortunate. I think the major thing that we see is autism--people have associated vaccines with autism. Now we're beginning to see that there are probably genetic causes of this, and vaccines have nothing to do with it. Maybe the science will be strong enough 00:49:00that people will not link these two together anymore, but there absolutely is no link.

On the other hand, you can understand, Okay, if you get a vaccine and the next day you have a major migraine or something, you can say, Well, I had a vaccine yesterday and it caused migraines. There have been some really neat studies. Steve Black did one in [The] Lancet called "background rates." If you take a hundred thousand people and monitored them, so many of them will have certain very rare diseases, very uncommon diseases. If you take a hundred thousand people and immunize them, you're going to have those background rates in those people who get immunized. So that's why it's important to follow large groups of people to see whether or not these conditions that people get that are very rare really are associated with the vaccine. Most of the time in his study, it showed they're just background rates and had nothing to do with vaccine.

For instance, you say, Okay, I got my vaccine today and two days later I got hit by a car. Well, was there an association? Probably not. The same thing applies, Well, I got my vaccine and two weeks later I got transverse myelitis. Well, is there an association? Well, we have to look and see whether there was one, because potentially there could be, but the studies have shown that, No, probably even if you hadn't have gotten your vaccine you would have gotten that condition. So the background rates are very important for people to understand when you see these rare conditions following a vaccination.

TORGHELE: It sounds like there's always new pieces of information coming in to help make the decisions that you have to make.

PICKERING: Yes, absolutely. Unfortunately, a lot of times for conditions where we know there is no association, we still have to disprove it, so it takes a lot of time and effort. It's important to do because we have to show that there aren't these associations, but some of them are just so obviously negative it's 00:51:00unfortunate. Convincing people--some people have their minds made up that you just can't change them. For instance, just like the old superstition I told someone the other day. Walking down the street and if you see a ladder, will you walk under it? No, because I've always been told it's bad luck to walk under a ladder. It probably is because something might fall out and hit you, but it's the same feeling. You get this thing ingrained in you, and it's hard to change someone's opinion when it's so deeply ingrained. We just have to be patient and remember that not vaccinating children damages and injures the children, and we've got to help parents who may be anti-vaccine realize that. It just takes a lot of patience.

TORGHELE: And good explanations like you're giving. Going back to the ACIP and how that works, I was wondering if there were times when major organizations [that] are represented there had disagreements about how a vaccine is given or 00:52:00about timing or anything, and how that's handled?

PICKERING: There occasionally are disagreements. There are disagreements between members of the ACIP or members of the Red Book committee about specific issues, but that's the real benefit of an open meeting where these can be publicly discussed. I think that when you go back many years, the MMR [measles, mumps, and rubella] vaccine was one of the areas where there was disagreement between ACIP and the American Academy of Pediatrics, for the second dose. The second dose of measles vaccine was recommended to be given at ten to twelve years of age by the Academy, whereas the ACIP said it should be given around four to six years of age. That led to a disagreement, and finally they worked together. They're friends. They worked together and resolved the issue, so that it would be given at ten to twelve years of age. This resulted in the first harmonized 00:53:00immunization schedule. Before then, there were different schedules. They contained the same things, but they weren't harmonized.

Now the schedule, since 1995, has been harmonized. Now, what does that mean? Well, it means that the ACIP makes the vaccine schedule--makes the vaccine recommendations that are agreed upon by the liaison organizations, and if not agreed upon, they will comment on it. The vaccine schedule is also endorsed. It's endorsed--the child schedule is endorsed by the American Academy of Pediatrics, American Academy of Family Physicians and ACOG, the American College of Obstetricians and Gynecologists. Just as the recommended schedule has to be approved by the director of the CDC, the recommended schedule for the Academy of Pediatrics has to be approved by the board. Of course the COID first, and then the board--Committee on Infectious Diseases. The AAFP, American Academy of Family Physicians--that schedule has to be approved by their board, and same for 00:54:00ACOG and the nursing organization. So it's not just an ACIP schedule. It's a harmonized schedule between those organizations. The adult schedule, you have the American College of Physicians that signs off of [on] it, as well as ACOG and AAFP. So it's harmonized, they come together.

So the October ACIP meeting when the final recommendations are made--they're all added into the schedule, and then a very short period of time that the folks at ACIP have to get all these approvals makes it be published in February, and it's published the same schedule in MMWR, our wonderful MMWR. It's published in Pediatrics, it's published in the ACOG journal, AAFP journal. So all the journals will publish the same immunization schedule, and that's been going on since 1995. It took a little work to get there, but we are there now, so there's no disagreement. All of these organizations agree with the schedule, every year.

TORGHELE: Do they do it in an annual meeting? How is that done? How do they show they agree?

PICKERING: What happens is that at the ACIP meeting the final schedules are discussed--they're presented, both the childhood and the adult schedules with all the changes. All the changes up until that meeting have been discussed, but there will be a few that will be added. At that meeting, the liaisons from these organizations and the liaisons to the ACIP will agree with all those changes. They make suggestions if they don't like the wording, and at the meeting then that wording is worked out. So there is fine-tuning. Someone may not like an adjective, so they'll add another one and they discuss it. So the approval of the harmonized immunization schedule every year is done in October by the ACIP, the liaisons. I haven't mentioned who's on ACIP, but there are pediatricians, 00:56:00family physicians, obstetricians, a nurse, a community representative, experts in epidemiology, statistics. All the expertise that you need is reflected in the membership.

Then what happens is that the liaison members take the schedule back. For instance, the liaison to the American Academy of Pediatrics takes the schedule back to the Red Book committee and then it goes to the board of directors of the American Academy of Pediatrics. Generally, they may have some questions, but generally they're kept up during the year with changes that are made, so generally there are a few little hitches that have to be worked out. They always are--we get under the gun and it gets published in February.

It used to be published in January after the October meeting, but it was just too much work and not enough time to get all of these changes made, because the schedule is very complex, as you know. That's the neat thing. These groups work together to unify. It's been done since '95 and hopefully will be done forever. 00:57:00That's the only way that we can do this with this complicated schedule. You can imagine what would happen if the American Academy of Family Physicians didn't have the same schedule as the ACIP, which was different from the Academy of Pediatrics; that would be a disaster. A lot of very smart people work together cordially to make sure that doesn't happen.

TORGHELE: The consistency of the recommendations would be very important.

PICKERING: Yes, very important. And they weren't always that way, but now they are, and that's good.

TORGHELE: So we touched a little bit about eradicating polio in the world, and I wondered if you had some thoughts about that?

PICKERING: Well, my thoughts are, Yeah, it's going to be done. There are a lot of obstacles. You're not just talking about eradicating a disease in a community or a state in the United States or the whole United States. You're talking about countries throughout the world, many of which have major, major problems. I 00:58:00greatly admire the vaccine givers. The people who administer polio vaccines go from community to community in these countries where they're war-torn and impoverished; it's horrible. These are real heroes, the individuals that are doing that. Hopefully, we'll get to the stage where all of polio will be eradicated, and in the future global eradication will be something that we can all be very proud of. We can be proud of the people who have done it, as well as the fact that they have done it. It's going to be done, but it just takes a lot of time and effort. And there's also hiccups that occur along the way--that you think you're there, and something else happens. There's a lot of really dedicated people who deserve a lot of credit for the work that they're doing.

TORGHELE: That's a good place to try to start wrapping up here. I wondered if you had anything that we didn't cover that you wanted to talk about, or any final thoughts before we finish up?

PICKERING: Well, I think that with regard to being at CDC, I would like to say a final thought about CDC. It is a real treasure in the United States. The public health aspects and the laboratory aspects are phenomenal. And many people throughout the country may not realize that people in the field of medicine--that you have a real complicated patient, you can talk to your local infectious disease person, but there's always an expert, generally an expert in that area if you need further discussion or if you need laboratory work done. The laboratories here are phenomenal. I can only touch on what all they do. I don't even know everything that they do. There's so many good things that are done. MMWR gives you a peek into all the many things that go on at CDC because all of the various branches that publish articles there. Working with EIS [Epidemic Intelligence Service] officers and the staff at CDC is a real 01:00:00pleasure; always willing to help anyone. That's a positive activity--and I'll just stress again, get into MMWR. Get it sent to you electronically, and you'll begin to see the real magnitude of what goes on here.

TORGHELE: That's a wonderful summary of what CDC does and what it can do when people are aware of it. I just want to thank you so much for all your input. You've provided insight into, especially, ACIP and vaccines that we wouldn't have had otherwise. Since you are sort of our expert on ACIP, can you tell us how people who want to learn more about it can get information about it?

PICKERING: Sure, thank you for asking that. The ACIP has a website. You can go to www.cdc.gov and then in the upper right-hand corner you can type in "ACIP," and it's amazing the information that's there. The charter's there. Each of the meetings webcasts can be shown. The minutes are shown, so you can look at the 01:01:00minutes. All the slides from the presentations are shown. So you can watch the ACIP meeting if you can't watch it in person. You can watch it afterwards when you have time to do it. Information that you want to know about the members, where they come from. It's just a wealth of opportunity that is all open to the public and shows a real transparency of not only ACIP, but the ACIP process, and how these vaccine recommendations are made out in the open with the ability of the public to comment. I might also add that if you want to make a public comment and can't attend, you can write the comment, send it in. It will be either read, if it's not too long, and definitely would be put in the minutes.

TORGHELE: That's great information for people to have. Thank you for including that.

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