Steve Cochi - Session 2



CRAWFORD: Today is Friday, March 1, 2019. This is Hana Crawford for the Global Polio Eradication Initiative [GPEI] History Project with Dr. Stephen L. ["Steve"] Cochi [MD, MPH]. We're in Atlanta, Georgia at CDC [United States Centers for Disease Control and Prevention] studios, and Todd [F.] Jordan is our videographer. Thank you for being here. This is your third session pertaining to polio.

COCHI: Thank you, Hana. Glad to be here.

CRAWFORD: Great. Do we have your consent to conduct and record this interview?

COCHI: Yes, you do.

CRAWFORD: OK, great. I'm going to read a little bit--we were talking a few minutes before, but I'm going to do a bit of an introduction. This is the third oral history you've done pertaining to polio for the David J. Sencer CDC Museum. First was with Karen Torghele on early polio for the Global Health Chronicles, and the other was with me for the GPEI History Project. Today is our second session, and I was hoping we could focus on the years 2001 to roughly 2014. Just to summarize a bit from the last session, we spoke about the beginning of the polio eradication activity at CDC and the acceleration of the polio program during the '90s. We also talked about building momentum through publicizing successes. We talked about immunization campaigns in China and the European region [of the WHO, EURO], especially Operation MECACAR [Middle East, Caucasus, Central Asian Republics, and Russia; currently MECACAR New Millennium], and we talked about the end of transmission of wild poliovirus in the Pan-American and Western Pacific regions [PAHO and WPRO], so in short, the acceleration of the program. To open up, could you talk about what was happening right around 2000?

COCHI: Certainly. Let me set the scene, because it has a lot to do with what we encountered in the first decade of the twenty-first century, which was quite different than in the 1990s. In the last segment, we did talk briefly about how there was an acceleration of activities with polio eradication. Just as the starting point, let's go back to 1988 where we had 125 endemic countries, about 350,000 cases. Over the course of the next twelve, thirteen years, we managed to get down to only ten endemic countries by the end of 2001, and we were down to between a thousand and two thousand cases per year, so it was a remarkable achievement.

Now, how did that happen? As a backdrop to this, you can just imagine the sense of optimism that we had going into the twenty-first century. A hundred and twenty-five endemic countries down to ten endemic countries in the very beginning of the twenty-first century. Well, most of those countries had relatively high-performing immunization programs: they had relatively high vaccination coverage with polio vaccine and other vaccines, and it turns out that with a strategy, a general strategy, of implementing three years of national immunization days, two national immunization days per year, poliovirus would just melt away in most of these countries, so we were really riding high. These were the low-hanging fruit countries, if you will, and so, by the turn of the century, we were down to these ten countries that were endemic, and the budget at the turn of the century was around $100 million per year. Now that might sound like a lot of money, but it pales by comparison to the $1 billion per year budget that the polio eradication initiative has had for the past several years.

What made it successful in addition to the fact that these countries were relatively-high performing? We had some very important initiatives. You mentioned MECACAR, which was an initiative that combined the ten countries from the European regional office of WHO [World Health Organization] and the bordering countries in the Middle East, so the Eastern Mediterranean region countries, which collaborated--these eighteen countries collaborated on cross-border immunization, on synchronizing their national immunization days, and that project MECACAR began in 1995, and by the end of 1998, there were no more cases of polio in the European region of WHO, and polio cases were markedly reduced in the Eastern Mediterranean region. Unfortunately, there still are cases in the Eastern Mediterranean to this day because of Pakistan and Afghanistan, so that was a very important initiative.

Also in the mid-'90s, under the leadership of Nelson [R.] Mandela [LLB], something called "Kick Polio Out of Africa" began, and all of the polio-endemic countries signed up to this program of doing at least two national immunization days per year through the end of the decade and into the first part of the 2000s, and it was a very successful advocacy program. Setting the scene for you, there was a lot of optimism by 2001.

CRAWFORD: I wanted to ask you about the choice of WPRO [WHO Regional Office for the Western Pacific] as a second focus area. Could you talk about how that decision was made?

COCHI: Yes, that's a good question. Of course, the first focus region was the Americas, Pan-American Health Organization [PAHO], which actually started it all with an initiative to achieve regional elimination of polio. In 1985, they began that with a target date of 1990 and came very close to that--the last case occurring in Peru in 1991. Now, the Western Pacific Region of WHO was targeted next, and your question is, why so? Namely because, number one, there was a lot of commitment to going forward, including the leadership of the regional office of WHO in Manila [Philippines]. Most of the countries were high-performing countries, although there were five or six countries that had relatively weak immunization systems, but not nearly on the scale as some of the weak immunization programs in Sub-Saharan Africa. It was a doable job, and most importantly, perhaps, China was on board, the most populous country in the world, 1.3 billion people. Not long after the commitment of that WHO region, China interrupted polio transmission in 1994, so it was a marvelous success story to move the program along in the Western Pacific Region.

In fact, the last case in the Western Pacific Region occurred in 1997, I believe, in Cambodia, near the Vietnamese border along the Mekong Delta. There's an interesting story there where the main reason why those were the last few cases of polio was that it was the children who were living on boats who were, in earlier rounds of polio immunization, being missed, until it was discovered, really--I don't know why it took so long to discover this, but we finally discovered that these boat people and their children were not being reached with polio vaccination, so the operational strategy changed entirely, and it didn't take very long after that for the last case to occur in Cambodia and in the Western Pacific Region.

CRAWFORD: Do you know if there are any stories about challenges with cross-border immunization in PAHO?

COCHI: PAHO and cross-border immunization: I think the main battleground there was in Central America. If you think back to the mid- to late-1980s, there was civil war in El Salvador, in Nicaragua, and there were some difficulties and some challenges really in coordinating cross-border vaccination. That really was overcome in large part through what were termed "days of tranquility." These were the first days of tranquility in the program and in the world where there was negotiated peace for a period of time so that vaccination could occur in all the countries, including, and along the border--the borders of these countries, and it became a very successful program strategy and endeavor, and it has been duplicated countless times in other parts of the world and continues to this day. It really cemented the concept of how important it is to do synchronized polio vaccination on both sides of the border of countries, because you have to reach the mobile population, either on one side of the border or the other. Do it simultaneously, and then you have the best chance of vaccinating every child, rather than if you're not doing it simultaneously, then a child from a country that hasn't done the polio campaign might slip across the border after a campaign has been done in the bordering country, leaving unvaccinated children from that mobile population, so that's a tried-and-true strategy of polio eradication. It's also been adopted in other vaccination mass campaigns, especially, for example, measles campaigns.

CRAWFORD: We were talking about cross-border immunization and how that has been applied time and time again. I was wondering if you would consider the Mekong River Delta an example of that--and MECACAR.

COCHI: Exactly. Those are all examples, and in fact, the Kick Polio Out of Africa initiative was also characterized by synchronizing the polio national immunization days across bordering countries, and as a result, these events, whether it was MECACAR or Kick Polio Out of Africa, hundreds of millions of children were vaccinated in, say, a week's time--[for] each round of these activities--so it was a public health measure conducted on a grand scale that had never been done before. Since that time, we have continued that pattern of very large-scale mass campaigns in [geographically] connected countries.

CRAWFORD: I wonder if you could talk a little more about the Kick Polio Out of Africa Campaign, just because we haven't recorded much about that yet.

COCHI: Well, the main thing, I think it captured the interest of the public, because of course, football--we call it "soccer" here in the U.S.--but football is sort of the national sport and passion of virtually every country, and in sub-Saharan Africa, and so the logo, all of the advocacy materials had the soccer ball as part of the logo with a person about to kick the soccer ball, and it really caught on fantastically, and there were press conferences and public events to really promote [these events and the polio campaigns]. Rotary [International] distributed many, many soccer balls in the course of these various events, and of course, with Nelson Mandela at the helm as the chief spokesperson, that was a home run, to use a [term from a] different sport from football.

CRAWFORD: That brings us [to] around 2000. I know that by 2002 in the last session you said that the program was down to ten countries.

COCHI: By 2001, we had ten endemic countries by the end of 2001, yes. Now, let's take a look at those ten countries. I had mentioned a few minutes ago that we had picked all of the low-hanging fruit, and we had had a great deal of success, leaving ten countries that by-and-large--most of those countries had large populations, were poor countries, low-income countries--had weak immunization systems in at least part of the country, or even most of the country, if not all of the country. Routine immunization coverage was low and not improving. That means that you're building on the routine immunization system on the basis of pretty low population immunity against polio, so it required you to do more polio mass campaigns. You couldn't get away [with what we had done] in those earlier countries with just doing two nationwide polio mass campaigns per year to get the poliovirus circulation to melt away. It required more resources, not only because you had to do more polio campaigns per year, but most of them were large countries, very resource-intensive. The countries I'm speaking about included Nigeria, Pakistan, Afghanistan, and India.

Nonetheless, by the end of 2005, we were down to only four polio-endemic countries. From ten in 2001 to four by the end of 2005, the beginning of 2006, so we were still making progress. The problem was, there was still a lot of polio disease burden in those four remaining polio-endemic countries, and I just named those four countries. I don't know if I had said this in the earlier tape, but we called them the "PAIN" countries.

CRAWFORD: As an acronym?

COCHI: As an acronym. Pakistan, Afghanistan, India, Nigeria. They caused the program a lot of pain and have continued to cause the program a lot of pain as we can talk about going forward. A big part of this problem was, not only was it a challenge to interrupt polio circulation transmission in these four countries, these four large countries--poor sanitation, which also increased the propensity for the virus to circulate; tropical countries, as well, and the oral polio vaccine doesn't work as well in tropical countries. But these countries also were sources of exportation of poliovirus to neighboring countries, and even distantly. Not only do we have these four endemic countries, but surrounding countries where we had managed to stop transmission, [and to] make them polio-free countries, were subject to repeated importations of poliovirus from these four remaining endemic countries. We had to deal with, over the course of the next ten to twelve years in the first part of the 2000s, we had to deal with, [on an annual basis,] eight to nineteen countries that were previously polio-free that got re-infected through importation of poliovirus from these four remaining endemic countries--a real diversion for the program, a real source of requiring more resources. Ultimately, we tabulated it up through about 2014, and there were forty-three different countries that were previously polio-free [that] were subject to importation events. More than ninety importation events occurred in those forty-three countries, so some countries had more than one importation event, causing an additional nearly four thousand polio cases, and at a cost of well over $1 billion, in addition to what was being devoted to those four remaining endemic countries.

The program had to expand both in resources and in the number of staff who were involved in polio. In fact, there was about a ten-fold increase from the early 2000s to about 2010, in the number of polio staff that were deployed, and they had to be deployed to these countries that were at risk that surrounded the four remaining endemic countries. It was a difficult decade, is what I'm leading up to, a challenging decade, a decade in which the case count was up and down, up and down, but basically over the course of the decade, it stagnated. Some critics were coming out of the woodwork by the end of the first decade of this century: "Can you really stop polio?"--can you really stop polio, in spite of the fact that we were down to those four endemic countries. We really had to modify strategy and start paying more attention to these polio-free countries that were vulnerable and at risk to become re-infected and do multiple rounds of polio campaigns in those countries, as well, which stretched the resources, stretched the staffing as I was alluding to a minute ago. To make it even more challenging, those four endemic countries were subject to a lot of civil unrest, conflict, even war. We're talking about Afghanistan, for example, the emergence of Boko Haram in Nigeria, instability in Pakistan, especially along the border with Afghanistan, and some of the other countries that surrounded the endemic countries that were vulnerable, included South Sudan, Somalia--very challenging countries because of civil unrest.

There was one event that occurred that was especially challenging and damaging to the program: in northern Nigeria, for an entire twelve months, from about mid-2003 to mid-2004, because of misinformation that was emanating from some of the religious leaders and got picked up by political leaders in northern Nigeria, that the oral polio vaccine was unsafe--it was causing HIV [Human Immunodeficiency Virus] infection; it was sterilizing your children; we should stop using the vaccine until there's some testing of the safety of the vaccine by a trusted Muslim organization.

For an entire year, polio vaccination stopped in northern Nigeria. It was like a wind wheel, just poliovirus spewing out of Nigeria, and more than twenty countries became re-infected across sub-Saharan African, all the way to the Red Sea, and even went across the Red Sea, infecting Yemen and Saudi Arabia in small numbers, and even distantly to Indonesia, which we presume may have been an importation that came from the Hajj--from Indonesians visiting Saudi Arabia for the Hajj and then bringing the poliovirus silently back to Indonesia. So, this was a real setback for the program that we had to overcome.

CRAWFORD: From Mecca [Saudi Arabia] to Indonesia.

COCHI: That's right.

CRAWFORD: Could you talk about the response, or maybe before talking about the response, could you anchor us in your day-to-day? Where were you and on the daily basis, what was your work like?

COCHI: I have been Atlanta-based and leading the program until recent years, first as the division director of the Global Immunization Division [GID], then as a senior advisor, which is my current situation. My immediate answer to where was I: I was either on a plane or out in the field in many different countries and regions, because we still had hotspots and problems in many parts of the world. There was a real need to strengthen our partnership, to reassure the faint-hearted that we were still moving forward, despite the setbacks, and to advocate to help with resource mobilization indirectly. Rotary International was the main engine for that, really. Yes, so I was all over the place. [Laughs]

CRAWFORD: I've heard that you have a lot of miles. You mentioned that the last time we spoke, just speaking to just how much traveling [you do].

COCHI: I don't know if that's something I should be proud of it, or whether it brings with it some notoriety, but I've just since in the last twenty-five years or so, I've accumulated more than four million Delta miles. Just the thought of it kind of makes me feel a little tired. That's what it took, and that's what it takes. We've had no polio in the Americas since 1991, so we have to go where the action is. We supplement [the short-term assignments of our Atlanta-based CDC staff with long-term assignments of our CDC staff to priority positions within WHO, essentially] loaning [CDC] staff to WHO regional offices and key countries to work on the scene [and on the ground on a daily basis] with their counterparts on the WHO side [and within the Ministries of Health of the host country]. It's a lot easier and more productive, I think, for our staff to be in-country where the action is.

CRAWFORD: I'm thinking about the response and changes, and the program and resources that became activated, but I'm also thinking about the STOP [Stop Transmission of Polio] program, which kind of predates where we are right now. It's in 1998, right. I wonder what role STOP played. Could you speak about that a little bit?

COCHI: STOP began--I think we sent the first cadre of people out into the field in January of 1999, and we were organizing in 1998, with the great support of the then CDC director [Jeffrey P.] Jeff Koplan [MD, MPH], and the purpose of STOP was, we were realizing that even before this resurgence of re-infected countries, there were a lot of outbreaks. There were a lot of needs out there in the developing countries, and at that time, there were very limited staff in-country. We said we need an industrial-strength solution to getting more staff out into the field, to help at least on a short-term basis. We created the STOP program, which means "Stop Transmission of Polio," and began training mid-level professionals, some from CDC, but really from all over the world. The first class was only about twenty-five, thirty people. [We did three such deployments per year, each of three to four months' duration]. [The STOP program] has grown [tremendously] over the years to our [currently] deploying [approximately 250 persons] for [eleven-month assignments]. [It] has really bolstered the forces on hand in-country for the ministries of health, for WHO and UNICEF [United Nations Children's Fund] on the ground. Many of these mid-level professionals have gone on to get hired, promoted in jobs in their own ministries of health, hired by WHO or UNICEF to work in polio [or] in other immunization areas, so we're very proud of the STOP program [as a capacity-building activity]. We've trained well over two thousand individuals cumulatively, and they've gone out on, maybe on the order of 3,500 to four thousand assignments, so some have done repeat assignments. It's been a fantastic capacity-building venture.]

CRAWFORD: What happened in 2001? Been through the scale-up and the acceleration of the program, down to ten endemic countries. Are there changes in strategy? What happens?

COCHI: Very good point. Well, we had to change strategy, and we had to look at whether there were some new tools or innovations that we could employ. First, on the program implementation side, we had to learn more about what it took and what it takes to reach previously unreachable children, because of insecurity, because there were underserved populations, minority groups, mobile populations, migrants, nomads--or sometimes if there was a minority religion, like in northern India, there were suspicions on the part of the Muslims in India about the vaccine and about the intentions of the government of India that had to be overcome. To take that one up, we learned much, much more about the non-scientific side of things, which by that I mean learning to engage communities, learning to get their trust, learning to get community leaders, religious leaders involved in the program, speaking on behalf of the program to mobilize communities, to build trust. It was years in the making, but it had a tremendous impact over time.

Also--and India's probably the best example about how to reach mobile populations. They brought it to a fine art, because India's a country--1.2 billion people--where the population is always on the move. You have migrant workers who work in the brick kilns, or in agriculture, who are living in one location for one part of the year, and then over here to do the harvest in another part of the year. India was able to map thousands of communities of migrants and where they lived which part of the year and target those communities during the mass campaigns. During the mass campaigns, they blanketed the trains. They blanketed buses, boarded the trains and buses, to get every child that looked like they were under five years old two drops of polio vaccine, and it was a remarkable program, and it was remarkably successful, and finally led to the last case of wild virus polio in India in January of 2011. Those are some of the program implementation changes, lessons learned that we benefited from.

We had to strengthen the surveillance system over time to get a better picture of where polio was happening and where it wasn't happening. On the laboratory side, they were always developing new diagnostic tools that would make it easier for the laboratory side of the program to successfully perform their work, to get a result earlier, you know quicker, so that the intervention, if needed--the polio vaccination could take place earlier and sooner in time, before any outbreak grew in size.

CRAWFORD: We were talking about India and some of the innovations, new implementation strategies.

COCHI: India was a good proving ground for these innovations, but they spread widely. Also, being able to measure true coverage by developing a system for monitoring, where there were independent monitors and ways of measuring coverage that weren't subject to the vaccinators themselves, or the program people, perhaps falsifying the information a little bit, so that it looked better than it really was. These and other implementation measures were major changes in strategy. Another one I should just mention is using the International Committee of the Red Cross and political leaders where needed to negotiate cease-fires or truces, and this really became an essential item in some countries. For example, in Afghanistan, until very recently, the Taliban in Afghanistan participated in the program. As long as they had the assurance--and we developed trust that we would give the Taliban leaders the vaccines for the communities that they controlled; they would choose the vaccination teams; they would go and do the vaccination, and everything worked out--

CRAWFORD: How did you know?

COCHI: --so we had a lot of success because of that. Because even the Taliban saw that good health is good politics, and they were trying to serve the communities that they controlled, because politically, that would enable them to have a better chance of maintaining control of those communities, politically.

CRAWFORD: Who was managing those relationships?

COCHI: There was a lot of decentralization of this. It was managed by the Eastern Mediterranean Regional Office, and at the country level by the heads of the WHO and UNICEF country offices, and the respective political leaders and ministry of health officials in Afghanistan. A lot of it was done very quietly [behind the scenes], but it was quite successful.

With these implementation changes, we were able to continue to make progress, even though we weren't able to get across the finish line.

In addition to that, I had mentioned that the laboratory developed new diagnostic tests that improved the surveillance capacity. We also tried to address the problem of trivalent oral polio vaccine [tOPV] not working well in tropical, developing countries, and was there a way that we could develop a tool that would get around that? There was a fair amount of difference of opinion about this and how we should go forward.

To step back--and I don't want to get into too much technical detail, but the trivalent vaccine, as its name suggests, it has three components: types 1, 2, and 3 poliovirus. The type 2 poliovirus is the strongest; it outcompetes the types 1 and 3, in general, for establishing infection in the intestinal tract, and that's how you acquire protection or immunity against the poliovirus. You have to get infected with all three of those over time to acquire immunity against all three. Because of this competition, it takes multiple doses in most children, and the type 2 was so good at competing that we thought, if we could remove the type 2, then dose-for-dose, the vaccination might improve the protection against type 1 and against type 3, either individually, or if they're both given together. We were interested in going forward with this, because the last case of wild type 2 polio was in 1999, so we were continuing to use the type 2 poliovirus in trivalent vaccine and causing vaccine-derived poliovirus [VDPV] outbreaks occasionally and causing your garden variety vaccine-associated paralytic polio [VAPP]. "Gee," [we asked ourselves], "[should] we develop either monovalent type 1, type 2, and type 3 products that would work better by themselves, or a bivalent [vaccine containing types 1 and 3 viruses]?" Part of the controversy was that those of us at CDC, starting in the late 1990s and carrying on into the early 2000s, we were strong proponents of just [taking] out the type 2 component and [using] bivalent 1 and 3, since we had seen the last case of type 2 polio [in 1999]. That way, for every round of vaccination, we were providing [increased] immunity against both types 1 and types 3, rather than resorting to just using the monovalent type 1 for a campaign, and then sometime later, using the monovalent type 3. You'd have to do two campaigns [using the monovalent products] instead of one [campaign]. [Bivalent vaccine also had the advantage that] the type 1 and type 3 [components] didn't really compete much with one another; they did pretty well [together]. As long as that type 2 was gone, [the bivalent vaccine] did pretty well, dose-for-dose. [However, we lost the argument, and the policy implemented in 2005 was to use monovalent instead of bivalent vaccines selectively for polio mass campaigns.]

CRAWFORD: Later, bOPV [bivalent oral polio vaccine]--

COCHI: In the early going, we lost that struggle. What happened--first, it was an incremental decision that WHO made. Let's get the monovalent polio vaccines relicensed, because they were licensed way back in the 1960s and used. It was easier to dig up that old documentation and licensure and convince regulatory authorities to go ahead. These were safe products back in the 1960s, so we'll just relicense them. That's what happened, and beginning in 2005, monovalent types 1 and types 3 were used, but especially monovalent type 1, because that was most of the remaining polio in the world.

The downside is, if you use monovalent type 1 vaccine repeatedly and don't use the type 3, then your immunity gap [to type 3 grows] over time in that country, and that's what happened. We had outbreaks of type 3 polio that resurfaced, so it was like a ping-pong effect, and late in the game in India in 2009, 2010, there was an outbreak of hundreds of cases of type 3 that we think could have been avoided if we were using the bivalent vaccine. We had to wait until 2010 for the bivalent vaccine to come along. It was a five-year period between when the monovalents became widely available and were used in the billions of doses, and 2010, when bivalent vaccine became available.

CRAWFORD: I'm confused about why monovalent preceded bivalent OPV [oral polio vaccine]. You said that the monovalent vaccines were being relicensed, so was it more convenient?

COCHI: Well, bivalent vaccine was never licensed and used. [In the late 1990s,] WHO [hired as a technical consultant] a very distinguished regulatory authority [and expert on vaccines, Dr. Paul D. Parkman, MD] from the FDA [Food and Drug Administration to review existing data on the safety and immunogenicity of bivalent OPV and render an opinion on whether WHO should go forward with having the vaccine WHO-prequalified and licensed for use]. [Dr. Parkman] was retired [from the FDA] at the time. [His] report said [that] to demonstrate the safety of the bivalent vaccine, you would need to do trials that might involve as many as millions of children. [This was totally] infeasible. Common sense would make you think, knowing that the type 2 virus in the trivalent vaccine was one of the two leading causes of [vaccine-related] paralytic polio [the other being the type 3 vaccine virus]--vaccine-derived paralytic polio [and] vaccine-associated paralytic polio--[that with removal of the type 2 component, the safety of the vaccine would increase]. If you took the type 2 out [of the trivalent OPV], wouldn't you have a safer vaccine than trivalent? That logic and that common-sense reasoning didn't win the day [however].

CRAWFORD: Understood.

COCHI: We had to do it incrementally and get the monovalent [vaccines] relicensed, go through this period of five years of ping-pong effect, use the type 1, and then the type 3 polio starts reappearing. Then you use the type 3, couple of rounds, then the type 1 would start rearing its ugly head.

CRAWFORD: One of the strains--I don't remember whether it's type 1 or type 3, whereas typically, what I read is that one in two hundred cases will cause paralysis. Is it type 1 or type 3 that's one in a thousand?

COCHI: It's type 3, yes. Type 1 is the one that is about one in a hundred, and type 3 and type 2 are more in the one-in-a-thousand range, so it averages out to one in two hundred susceptible children.

CRAWFORD: That immunity gap five years later, was that a gap in type 1 and type 3, or were there--

COCHI: It was more a gap in type 3 and to some extent type 2, which we can get into in a minute, because disproportionately, the type 1 monovalent was used, since that was the prevailing wild poliovirus that still existed. There was much, much less type 3. We created a situation where more type 3 polio emerged than otherwise would have, because we were only using the monovalent type 1 vaccine, time and time again.

The other downside of this is, you know, when you get a new tool, everybody thinks, oh, this is the solution. This is the magical solution. I think there was too much abandonment of using the good old trivalent oral polio vaccine, which was necessary to use to make sure that type 2 immunity remained high. If you only went to using monovalent 1 and monovalent 3, type 2 immunity would drop, and in fact, that's exactly what happened in the countries that overused--in my opinion--the monovalents, and chief among them: Nigeria.

Type 2 vaccine-derived polioviruses emerged in Nigeria in 2005, and they've never completely disappeared. Hundreds and hundreds of cases of vaccine-derived poliovirus that would not have occurred if we had just used trivalent oral polio vaccine for some campaigns, intermittently, between using the monovalent--but there was this rush. There was this almost obsession to use monovalent type 1 [in campaigns]--do another one, do another one--creating immunity gaps against both the type 2 and the type 3, yes, which came back to haunt us. There was some substantial difference of opinion between the CDC folks and the WHO folks about this strategy. Bivalent finally won the day in 2010, but I think we lost a lot of time in the interim. That's the way it goes. [Laughs]

CRAWFORD: Could you talk about monovalent type 2 vaccine that's used? It has to be used with the permission of WHO?

COCHI: Yes, fast-forwarding to more recently, for reasons that I had described earlier with no type 2 polio in the world, why continue to use the type 2 oral vaccine? In 2016, there was a switch [worldwide] from using the trivalent OPV to using the bivalent 1 and 3 OPV.

CRAWFORD: The switch over a month's time.

COCHI: In the entire world, over a month's time--I think it was like 126 countries that were using trivalent oral polio vaccine, stopped using it and replaced it with the bivalent vaccine. We still needed to have the monovalent type 2 OPV in reserve for the potential emergence of the vaccine-derived type 2 outbreaks, and we've had a number of instances of those outbreaks occurring since 2016 that have required the mobilization of these stocks, this reserve of monovalent type 2 OPV to target specifically that type 2 outbreak. It's a type 2 vaccine to target the type 2 outbreak--very specific.

Then, after the type 2 vaccine was used to control and terminate the type 2 vaccine-derived poliovirus outbreak, we didn't want the type 2 vaccine to continue hanging around, so we had to make sure that any unused vaccine was taken back up. Otherwise, you would be introducing the type 2 vaccine virus in the population on an ongoing basis, and you might actually start up another vaccine-derived type 2 poliovirus outbreak. It's somewhat complicated, but these are some of the machinations that we had to go through and continue to have to.

CRAWFORD: I'm shifting through time. Sorry, I just jumped ahead. [Laughs] To go back to 2005, monovalent vaccine, and then trivalent vaccine, as well, could you talk about the landscape of the global program--who was in leadership--and just kind of lay out the scene that way within the program?

COCHI: At that time in 2005, still there were the four spearheading partners: WHO, Rotary International, UNICEF, and CDC. Many other partners, NGOs [non-governmental organizations] and so on, were stakeholders and partners. It had grown tremendously in size, but still, there was inadequate budget. What I mean by "inadequate" was that we were living kind of hand-to-mouth. We didn't have a budget that was raised in advance of a [one- to two-year] period so that we knew what resources were available and could plan [further] ahead. We were always planning with only a six- to twelve-month time horizon.

With the prolongation of the program, there was a lot of advocacy toward [William H.] Bill Gates [III], and he took an increasing interest in polio eradication, because he saw [the importance of achieving polio eradication] in the midst of his many contributions, both from an advocacy and a financing standpoint on global immunization, in general and helping in great part to fund the Global Alliance for Vaccines and Immunizations [Gavi, the Vaccine Alliance]. He saw that a success in polio eradication was essential to being successful in the broader sense, and so increasingly, he took up an interest, hired some staff that were detailed to work on polio eradication, and by 2009, 2010, he started investing more and more heavily in the program at a point in time when the program really desperately needed it, because we were already nearly ten years past the target date, of 2000, to stop transmission, globally. That was a great boost to the global program. Dr. [William H.] Bill Foege [MD], former director of CDC, had gone to work with the [Bill & Melinda] Gates Foundation way back at around 2000 or so, at the beginning of the Global Alliance for Vaccines and Immunization. He was a senior advisor to Bill Gates, and I think he was very influential in getting Bill Gates to understand how important this was. Bill Gates is still out there and playing a major role in advocacy to complete the job of polio eradication.

Another thing that really moved things forward, as I had indicated, [was that] by the turn of the century, we had had all of this success, and in fact three regions of WHO, about fifty percent of the population of the world, had been able to certify their region as free of poliovirus--first in the Americas [in] 1994, then the Western Pacific Region in 2000, and then in 2002, [four] years after the last cases in southeastern Turkey, the European region of WHO certified. We had half the world certified as polio-free. We still had South-East Asia, including India, that was not polio-free.

In January 2011, the last case of polio occurred in India, and three years later in 2014, the South-East Asia Region of WHO, which includes India, a population of more than a billion and a half people in eleven countries was certified as polio-free, so we went from fifty percent of the world to more than eighty percent of the world certified as polio-free by 2014. That was a major milestone because there were many critics out there that said, "You will never eradicate polio from India"--this huge population crowded into a relatively small geographic area, terrible sanitation in many parts of the country--tropical country, the vaccine doesn't work so well; you have to give many doses on average to protect a child against all three poliovirus types. You will never do it. We did it. I think that convinced even the critics at that point in time that polio eradication was achievable, because it wasn't that long ago, back in the 1990s--of the 350,000 cases occurring in the world at that time, more than half of them were occurring in India. That was a major step forward and takes us up to the end of the period that we're discussing today, [through 2014].

After the interruption of transmission of polio in India in 2011, we had to redouble our efforts even further. [Thomas R.] Tom Frieden [MD, MPH], [a huge advocate for polio eradication], had come in as the CDC director [in June 2009], and we were looking for a way to really mobilize resources, both human and financial, even further and get the world and our organizations, including WHO and UNICEF, to pay more attention, to get more momentum going, and so we put polio eradication in the emergency operations center [EOC] of CDC in December of 2011. That's another way of saying that when a program or an initiative goes into the CDC's emergency operations center, it becomes a priority that allows the CDC director and the program to draw resources, not just from the global immunization division, but throughout CDC, and that's exactly what happened. Within a month or two, WHO established its own emergency operations center for the same reason [in early 2012]. Going forward into 2012, we had redoubled our efforts and found new ways to get the program more visible on the global scale.

CRAWFORD: Since you brought up EOCs, could you talk about even past our timeframe for today, but the progression and development of emergency operations centers? Was the U.S. Atlanta-based EOC the first to be activated?

COCHI: The emergency operations centers and the whole concept of emergency operations, it's really drawn from the military, historically, in terms of how do you deal with a crisis--how do you deal with a disaster? Some of those methodologies were drawn into the emergency operations center concept. It's the same concept that is used in the U.S. and throughout the world, in terms of addressing hurricanes, tornados, floods. You see those emergency operations centers in your state or city going into operation when there's a weather disaster or some other kind of disaster, same general concepts.

In CDC, it really came into play after 9/11 [September 11, 2001 attacks] and after the anthrax scare and became sort of a routine modality for CDC to address health crises, outbreaks, or even non-infectious disease health crises. The Ebola crisis is the most recent example, as well as the Zika crisis, where CDC put those initiatives into the emergency operations center for a period of time to draw on the larger resources, human and financial at CDC. It's a concept that's been adopted by other organizations like WHO, by countries--those "PAIN" countries, they all adopted several years ago emergency operations centers for polio, not only nationally, but in the key provinces and states where the major part of the polio problem still existed. It's a concept that has taken hold, and as I was suggesting, it's not a polio-specific concept. It's something [whose] principles can be implemented for any health crisis very effectively.

CRAWFORD: That's important infrastructure.

COCHI: Exactly. As one organization, CDC, we continue to advocate for countries to generalize that concept of emergency operations centers as part of their health programs, far beyond polio. Even though there are limited resources, many countries have taken that up. That's a part of the global health security landscape these days as an important principle and an important priority.

CRAWFORD: Could you talk about the endgame, sort of right around 2012, 2013? I think at this point, and also there were--around that time, the first killings of vaccinators were happening. Is that right?

COCHI: Yes. Well, they're two pretty separate [issues], but let me start with the endgame. We started using that word and that concept--I think it really started taking hold after the success in India when we were really starting to smell the finish line. With Bill Gates getting involved, and the prospect of more resources for the first time, the program had the opportunity to lay out a five- or six-year strategy, a five- or six-year plan, and mobilize the resources to fund in advance--up front--most if not all of that five-year plan, so that we weren't playing the game hand-to-mouth, so that we could plan ahead and know what resources we had, one-year, two-[years] from now. It makes planning a lot more rational and implementation that much more effective.

Together, the five core partners, including the Gates Foundation, we put together an endgame strategy document for the years 2013-2018 and up-front resource mobilization to implement that strategy, which was based on a $7 billion budget for those six years. More than $5 billion [was] raised up front before the plan even began to be implemented in 2013, so that was a new way of working [compared with the previous standard of having to work within only a one-year budget horizon with all of the uncertainty that entailed. The flexibility of being able to implement the program in the setting of multi-year budget commitments already in hand was a tremendous improvement that] continues to this day, even though that [2013-2018] endgame strategy had as an informal target date the end of 2016 to stop global polio transmission.

Here we are in 2019, and we still have transmission in two countries, Pakistan and Afghanistan. The prospect [now exists], since we haven't had any wild polio in Nigeria since September of 2016, of Nigeria being certified as free of all wild poliovirus by the end of this calendar year or early 2020, in which case the entire region of Africa could also get a regional certification in 2020, so we're making forward progress, but as I think we'll talk about in the next session, there are enormous challenges in just snuffing out what little polio still exists in Pakistan and Afghanistan these days.

CRAWFORD: What difference does it make to be able to plan five years ahead and begin that planning with funding?

COCHI: It makes so much difference, because, number one, you can plan a future based on what you think is necessary, what is the right thing to do, rather than being limited, like we were previously, by the limitation in resources. You always had to make decisions that were compromises, sometimes serious compromises, about what you think would actually stop the outbreak, or make forward progress in Nigeria, because you didn't have enough resources to do what you really truly thought was needed to make that progress, or have that success, and so you could, up-front, do what you think would really get the job done for the first time, rather than being constrained by the limitations of what you really had in hand to be able to do less than an optimal job.

CRAWFORD: Could you give an example of what that would look like? I'm thinking about scale, like how difficult it would be even to scale out.

COCHI: I think just in general, you know, if the thought was, OK, in these four PAIN countries, they needed to do four, six rounds of polio mass campaigns per year, but you only had enough resources to do three, or two, then you would have to make that compromise and do something that you think would not get you to the desirable end. That's sort of an artificial example, but repeatedly, that's the way the program had to work even with increasing resources over the course of the first decade of this century. Always had to do something less than what we thought would guarantee a successful outcome.

CRAWFORD: I have a couple of follow-up questions, and one of them is about IPV [inactivated polio vaccine] in India. India finished off polio transmission using OPV. I wonder, I know that for a long time, there's been debate about IPV, OPV, the tools of polio eradication, and I wonder what it meant when India saw the last case--what it meant for the tools, and what it meant about the vaccine.

COCHI: I mean, this debate goes back to the debates and arguments between Albert [B.] Sabin [MD], who created the oral polio vaccine, and Jonas [E.] Salk [MD], who created the inactivated, or the killed, injectable polio vaccine. The case in point is India. They were successful using only OPV, and the reason why OPV was the vaccine of choice for them was it was so much less expensive. It was ten, fifteen cents a dose, compared to a dollar, two dollars, or even more per dose. Easy to administer. Volunteers could administer--all you had to do was be able to get a child to open his or her mouth and drop two drops in. Mass campaigns could be done in a matter of two or three or four days. If you had an injectable vaccine, then it would require skilled health personnel who were much fewer in numbers, and so it would take a much longer period of time. There were safety issues, and so on. You couldn't go house-to-house with an injectable vaccine; you could with the oral polio vaccine. A number of other reasons: India was successful without having to use IPV. They have introduced IPV since then, beginning in 2016, but they had to do so many polio campaigns per year in order to achieve that in the most high-risk northern states of India.

You're going to have people who say, "Well, oral polio vaccine was the vaccine of choice. They did it," didn't really need IPV. Then you're going to have proponents of IPV who say, "Well, if they had also used IPV, they wouldn't have had to do as many rounds of oral polio vaccination. It would have been less expensive. They could have interrupted polio transmission earlier."

Nobody will ever know. I think that debate will probably go on in perpetuity, but I think we've all come to the conclusion--or most of us, at least--that interestingly, in the endgame, both vaccines have a role to play, and that's exactly what the program is doing globally, using the oral vaccine, but also encouraging--and virtually every country has done so--the introduction [and] use of at least one to two doses of IPV in the routine infant and childhood immunization schedule. We're using both now, and they both have a role to play, which would be very interesting--since there was so much animosity between Jonas Salk and Albert Sabin--they might both be turning over in their graves right now. It would have been quite a wonderful event if they were still living and could come together and agree and embrace each other on the fact that both vaccines are now playing a role in the endgame. A lot of irony to that.

CRAWFORD: Could you talk a little bit more--we've talked about India, but the last case in India also was the last case in SEARO [WHO South-East Asian Regional Office], the whole region, South-East Asia Region. Could you talk about some of the other countries?

COCHI: It's an eleven-country region, more than one-and-a-half billion people. The other countries of the region--although economically and politically--with the exception of Indonesia, which is another very large country that's in the same region--the other countries are dominated economically and politically by India, this gigantic country. I'm speaking of Nepal, Bhutan, even Bangladesh, which is a country of nearly 200 million people, is somewhat dwarfed in comparison. They were sort of quietly going about their business, and they all stopped polio by no later than 2000, some well before that. They quietly did the job, and this dominating, sometimes domineering country, India, took another eleven years to get the job done, so there's some irony there.

CRAWFORD: That's another question I had about India. I'm trying to trace the theme of security and conflict, and just how that has been managed throughout the history of the program. Was security an issue in India?

COCHI: Security wasn't an issue in a large-scale sense, but for a period of time, and I alluded to this earlier, there was a great deal of mistrust among the Muslim minority population, which is concentrated in the states of northern India, and so there was some minor unrest related to that--there were trust issues. It was an underserved minority population, so there was some civil unrest, but it never grew to a large scale, but it did compromise the program until the program learned how to better engage these communities, build trust, get community leaders and religious leaders on board and participating actively and getting them to understand the benefits of polio vaccination for their children.

CRAWFORD: I wanted to ask you, too, what you remember about timing in the early efforts to engage leaders, like Islamic leaders in the program?

COCHI: Well, that was always occurring on some level, but it got accelerated, I think, in the midst of this decade of stagnation--in the first decade of this century--with continuing transmission and especially in Pakistan and Afghanistan. The Eastern Mediterranean regional office of WHO took some initiative to engage the Organization of the Islamic Conference, which is based in Medina [Saudi Arabia] and has broad representation from all the Muslim countries of the world--and to get them on board, use them as an advocacy organization and a trust-building organization. I think some of the main Muslim religious leaders in Egypt and other countries were also engaged.

It was a gradual process and continues to this day. If you look at the situation in Pakistan and Afghanistan, the mullahs and imams, huge efforts are made to keep them engaged in the program to make sure that they don't go to the negative side. That still happens from time to time, putting out fatwas saying that the vaccine is unsafe, but it's mainly at the local level.

CRAWFORD: I have two more topics on my list here. Is there anything else you want to add?

COCHI: Gee, I think I've really talked about quite a few things. I'm coming up with a blank right now, so what do you have?

CRAWFORD: That's great. The last two: I wanted to hear more from you about the endgame and strategic plan, and maybe how that compared to earlier strategic plans--and by strategic plan, I mean 2013-2018. Finally, I wanted to ask you about the story of declaring polio eradication a public health emergency of international concern.

COCHI: First, the endgame strategic plan: we would put together multi-year strategic plans over the course of the initiative, but the endgame strategic plan was probably our best work of art. A great deal of time and effort went into it by many people. I think it was especially important during that timeframe, 2013-2018, to convince partners, donors, to stay engaged--to continue to support financially--and from an advocacy standpoint, because we were so far past the 2000 target date. It also was particularly important in laying out what were we going to do differently in selected countries and areas that would get us across the finish line. What innovations, what changes in program strategy, and very important--all of it is very important, in terms of resource mobilization. It was by far the most solid strategic plan that we ever put together, and we had a whole string of strategic plans from 1988 onward to the present time. In fact, we're doing another strategic plan, since we're past 2018--sort of a bridging strategic plan that's about to be finalized--that once again is designed to focus mainly on, what are we going to do differently? What have we learned, and how are we going to use those learnings to do some things differently, and more successfully, to once and for all end transmission of polio in Pakistan and Afghanistan? With only a handful of cases, it's very frustrating to have this drag out so far, but when you look back at it, once India stopped polio, it's now been eight years where only three countries have had endemic polio transmission: Nigeria, Pakistan, and Afghanistan. Nigeria appears to have stopped transmission in 2016.

The tale of this polio eradication initiative is small and very prolonged, elongated, unfortunately.

CRAWFORD: Almost single-digits.

COCHI: [Laughs] Yes, unfortunately. What was the other?

CRAWFORD: The other one was the story of declaring polio a public health emergency of international concern.

COCHI: Yes. I was describing earlier that even though we got down to those four polio-endemic countries, we were having ten to fifteen countries per year that were previously polio free that were getting re-infected by importations from the endemic countries, and it was going on and on, and we had a bit of a flareup in 2013-2014. This was right at the time when the endgame strategy came into effect. There was a resolve that we couldn't allow this to continue without calling upon the International Health Regulations [IHR], a document that in 2005 all of the countries of the world--member states of WHO--had signed on to, that under these extraordinary circumstances a disease or an event could be declared a public health emergency of international concern. This edict, if you will, has only been used a handful of times, but we were able to convince the WHO director-general that polio eradication should be declared a public health emergency of international concern in 2014. There's a polio emergency committee that I serve on that reviews the situation every three months and makes recommendations to the director-general, but we have sustained the importance of continuing to call polio eradication a public health emergency of international concern until the last case.

CRAWFORD: I read a press release from 2014 that said--I think it was a unanimous decision to declare the public health emergency of international concern. Do you remember what led to that unanimous decision?

COCHI: I think there was just the realization that, again, we were having continued outbreaks in previously polio-free countries.

CRAWFORD: We were talking about what led to the unanimous decision to declare polio a public health emergency of international concern.

COCHI: Imagine the setting: it's 2014. We're nearly fourteen years past the target date. We've had the success in India stopping transmission in 2011, but we were continuing in the remaining three endemic countries to have poliovirus exported to ten to fifteen previously polio-free countries, and so there was the concern that this could go on in perpetuity, and we had to draw attention to this. We had to reconfirm the global commitment--to redouble that commitment--to finishing the job of polio eradication, so we convinced the director-general of WHO, and it didn't take much convincing to declare polio eradication a public health emergency of international concern.

It was a unanimous view of the polio emergency committee at that time, and we continue to have a consensus right up to today. We don't want to lay off the gas pedal at all. We don't want to give any even perception that this is no longer an emergency now, that we're down to just two countries and a handful of cases, and the world is spending close to $1 billion a year just to sustain how far we have come, and to let off the gas pedal, there would be undoubtedly this major, huge resurgence of polio in the world. It's very convincing, but it's frustrating to have time continue to march on.

CRAWFORD: We're in 2019 now. Could you compare your response to polio transmission having not been interrupted in 2000, and 2018, is there a difference in your personal feeling or response?

COCHI: Well, I think without a doubt, most people probably would say there's quite a difference. I think in the year 2000 or 2001, I was describing how even though we had missed the target date, there was a lot of optimism, because we had reduced the number of countries that had polio by so much, and we had prevented so many cases of paralytic polio--and I should point out that from 1988 to the present time, we prevented more than 18 million paralytic polio cases through polio vaccination, so that is a tremendous achievement. Still, if your goal is eradication, that means zero cases, so anything more than zero is a failure. From the perspective of someone sitting here in 2019, I think it's a little bit exhausting to think back, compared with the situation in 2001 where we were nearly there and feeling, with the optimism at that time, on the cusp of success.

CRAWFORD: Anything else you'd like to add today?

COCHI: That's it for today. Thanks.

CRAWFORD: All right, thank you so, so much.