 I'm very pleased to introduce Dr. Annie Rowe. She's originally from Northern California and trained. She got her MPH at UC Berkeley. I was actually one of her TAs at Berkeley. She did very well. Then she moved on. She focused on health and social behavior for her MPH and then continued with that concentration in her PhD at University of Michigan in Ann Arbor. She trained under Arlene Geronimus who is a leading expert in social epidemiology and immigrant health. Then she returned to California to our benefit. She's now at University of California Los Angeles as a postdoc. She has a highly prestigious and competitive UC presidents postdoctoral fellowship. That's a two-year fellowship at the Fielding School of Public Health. Annie's research focuses on social and economic causes of immigrant health trajectories. She focuses on ethnic minority immigrants, especially Asian American immigrants. Please join me in welcoming Dr. Angela. Okay. Maybe I'll get to see if my voice reaches the back. Thanks, Tim. Thanks for that introduction. First, I want to make sure if people in the back can hear me and whether or not I need to turn on the mic. You guys can hear me okay? All right. Well, thanks, again, for having me here. I'm really excited. This is my first time at UC Irvine and I'm excited to meet everybody here and excited to share some of the work that I've been doing. As Tim mentioned, I am a second-year postdoc at UCLA School of Public Health. If anybody's interested in the postdoc, I'd be glad to talk to you about it during lunch, after the presentation. Generally speaking, I consider myself a health demographer. What that means is I study these large-scale population-based trends. Within health demography, I'm interested in the health patterns of immigrants. I want to know what happens to the foreign born as I spend more time in the United States, what's going on in their lives that can impact their health. In my work, I take what's called a social determinants of health approach. This might be something that's familiar to a lot of you here. This is the idea that health is a state of well-being. It's a product of dynamic factors that range from individual-level lifestyle factors and includes social community factors, living and working conditions, and these broader socioeconomic and policy-level conditions. When we're thinking about immigrants, this means that we're concerned about individual characteristics, such as their English language ability or their development of their ethnic identity. We're also concerned about what their social lives look like, so how maybe experiences of racial discrimination or how their social networks are related to their health. We're also interested in their economic characteristics, so things as straightforward as income, more broadly speaking, their employment patterns or their working conditions. Finally, this also includes broader influences like policy, so how things like immigration policy or these larger historical trends of immigration can be connected to their health outcomes. To give you very briefly some of the stuff that I've looked at, I've looked at the relationship between racial discrimination and BMI and substance abuse. I've looked at how the relationship between income and health changes with longer residents among different immigrant groups. I've also looked at the effect of how timing of entry impacts the health outcomes of immigrants. Today, I'm going to be talking about a project I've done looking more specifically at the employment and working conditions of the foreign born and connecting it to their mental health well-being. Over the past year of my post-doc, I've become more interested in how the specific employment patterns of immigrants are related to their health. The project I'm presenting today looks at whether occupation mobility, pre- and post-migration is related to depression status of immigrants to the United States. Why am I concerned about occupation mobility? Why is it something that we should be interested in? Well, we know that one of the primary motivations to migrate is the opportunity to find good and adequate work. We also know that the act of migration itself is hugely disruptive on the employment patterns of immigrants. While they're very motivated to find work, their actual ability to do so is limited by things like language barriers, credentialing requirements, discrimination in the labor market, the absence of professional contacts. All of these factors can create these different conditions and employment conditions that immigrants face after they migrate. First, they can experience downward mobility, which means that their job in the United States is lower in terms of skills, prestige, or expertise than the job that they had in their country of origin. Migration researchers are actually very interested in this idea of downward mobility. An economist named Barry Chiswick and more recently sociologist, Ilana Ockress, has been studying this phenomenon of downward mobility. They find that it's something that's actually very common. I think for a lot of us, this is something that really fits in with the narrative, the immigrant narrative. It makes sense to us. The Washington Post actually recently wrote an article about downward mobility among immigrants, and they described it this way. The plight of those who are underemployed is familiar to anyone who has gotten a ride from a DC cab driver with an engineering degree from Ethiopia or had a car parked by a garage attendant who used to practice law in El Salvador. So this idea of downward mobility is something that's kind of familiar and intuitive to us, but there are other scenarios in which an immigrant can either maintain their pre-migration occupational status or even experience outward mobility after migrating. These scenarios are less studied, but we do know that sort of with this broader change in immigration policy that's starting to put more of an emphasis on employment based and student based visas. There are some immigrants who migrate and have sort of the resources and the infrastructure and the networks in place to sort of move upward in their occupational status. So while occupational mobility is really is very interesting to migration researchers overall, the health impacts of these trajectories haven't been explored yet. And I think this is a big gap in the literature because there is strong reason to believe that occupational mobility should have an impact on health. First occupational status is a key dimension of socioeconomic status, which we know is one of the most robust indicators of health. So for people who have higher education, more income and better jobs also tend to have better health outcomes. And the reason why this is is because these higher SCS individuals have more access to resources that promote healthy behaviors. They live in better neighborhoods, they have sort of more resource rich and supportive social networks, and they have better medical care. So if we extend this logic that higher SCS leads to better health, we might assume that upward occupational mobility would be associated with better health, because these immigrants may be earning more money and then have more access to these health promoting resources. Whereas downward mobility would be associated with poor health for the opposite reasons. But there's a growing number of researchers who have started to question actually whether improving SCS always leads to better health outcomes. So for example, Cindy Colin found that rising income was associated with better birth outcomes among white women, but not among black women. And what this growing group of researchers is starting to ask is whether for marginalized groups, if aspects of their social status can affect both the processes and outcomes of upward mobility. Now, while none of them have focused on immigrants per se, this does underscore the idea that for immigrants, stressors and barriers that arise from their unique social position can sort of play an important role, we might expect it to play an important role if we're examining the relationship between occupation mobility and health outcomes. And there is a little bit of evidence to support this idea. The only study that I was able to find that actually looked at occupational mobility and mental health was conducted in 1978 by Eaton and Lazzary. And they found that among their sample of West African immigrants to Montreal, both upward and downward mobility were associated with adverse mental health outcomes. So what I wanted to do in this study was sort of take this idea, but look at it in the US context, among a bigger group of immigrants, and among with more recent data. And what I'd like to suggest is that for immigrants, occupational occupational mobility gives rise to psychosocial mental health stressors that are distinct from resource related pathways. So if we're thinking about downward mobility, downward mobility can expose immigrants to things like poor job environment fit, or what I'm calling aspirational discrepancies. So job environment fit is an idea that's common in occupational health. And it's a sort of stress that arises when a worker's skill doesn't match that required of his job. When I say aspirational discrepancies, this is the difference between one's sort of economic and social goals and their actual reality. And this idea has been explored, a migration researcher named Wen Chuo has explored this idea in goals driving stress, and he found goals driving stress to be associated with higher depression rates among Chinese immigrants. For those who have upward mobility, they can be sort of exposed to a different set of factors. First, they can be rising into these higher status positions that have their own sort of unique job related demands. I'm Scott Sheiman, who's a sociologist at the University of Toronto has studied this sort of high the stress of higher status. But if you're thinking about immigrants, this is further compounded because they're adjusting to sort of new American work environments. And if you consider that they're working in these sort of upwardly mobile positions, they probably had to overcome a lot of barriers to get there. So not only language barriers and discrimination, but also sort of credentialing requirements and a whole host of things that may accumulate over time and take a toll on their mental well being. I don't think that this sort of downward mobility pathway is is that unexpected, it kind of makes intuitive sense. But I think what is a little bit different is this idea that upward mobility can actually be harmful. And I guess what I'm trying to say is that despite the sort of upward status in socioeconomic resources, immigrants might still exhibit poor health outcomes, because they're additionally contending with these barriers to their mobility. I'm also looking at differences across gender. We know that men and women differ in the kind of jobs that they have and their level of employment. But there are also different priorities and perceptions of work that are sort of wrapped up in gender roles. So for example, men who adhere to traditional ideas may feel more responsibility to provide for the family. And thus, so their occupational ability status might have more salient and they might feel more stressed or frustrated. In contrast, the work that immigrant women do, a lot of sociologists who study gender and work and immigration have suggested that the work that immigrant women do seems to be largely supplemental to the household. So Sylvia Pedraza calls this work necessary rather than self-actualizing. So many women may actually view their work roles very differently, which might result in differential relationships between occupational ability and health. So in light of these points in this literature, I have two hypotheses. The first is that immigrants who experience either an upgrade or downgrade in occupational ability will have more depression. And secondly, that this relationship will be stronger among men because of the salience of gender roles that might be wrapped up for men in work. So the data I used to explore these hypotheses is from a data set called the New Immigrant Survey. And this is a representative sample of immigrants who received their green cards in 2003. I use the adult samples. This is only includes people 18 years and older. I made several restrictions. First, I only included those whose first international move was to the United States and didn't make subsequent international moves. So this limited those with secondary migration, which I thought were likely to have different employment patterns. I only included those of working age and they had to have been employed in the country of origin and in the United States. So this left me with a sample size of 2,305. Here's some characteristics of the sample. We can see that the majority of immigrants are either coming from Latin America or Asia. The New Immigrant Survey does have a lot of detailed information about country and region of origin. But because of sort of the analysis I was doing, I looked at all immigrants together and controlled for region of origin and the multivariate analysis, which I'll show you. About a third of the sample, both men and women, are college graduates and 14% of those or so earned that degree here in the United States. And finally, this is a relatively new sample of, a recent sample of immigrants. Over 70% of both men and women had been in the United States for under 10 years. The health measure I used was depression. It was measured by Kessler et al.'s CD short form and you recoded as either depressed or non-depressed based on whether you met the DSM for criteria for depression in the past year. The depression rate was 2% for men and 5% for women. For a little bit of comparison, the depression prevalence among whites using the same scale was 8% for African Americans. It was 9% and for Latinos it's 11%. So this is much lower than some of the other national estimates that are out there that use the same scale. But remember that this is a sample of working immigrants. So they're likely to be healthier not only because they're working but also given their age. And also immigrants do tend to have lower rates of depression overall than the U.S. born. So sort of given those restrictions that are, that I put into the data that might reflect the low depression rate here. So I used two measures of occupational mobility and the reason why I did this was because I wanted to sort of capture immigrants' experiences in the labor market. But each of my measures sort of uses different standards of comparison to determine whether their post-migration job represented an upgrade or a downgrade. The first measure is change in occupational prestige. And this is measured by the Nikkei-Treyas score which is an established scale. And when it does it assigns every occupation a score between 0 to 100, 100 being the most prestigious job. And I took the difference between their post-migration. So this survey that I used had a lot of great information on their pre-migration characteristics. So I knew what their job was before they migrated. So I took the difference between their pre-migration and post- migration jobs to get a score. And I created three categories. The first was that they had no change in prestige. The difference between the pre- and post-migration was within a five-point range. So for example this is somebody who worked as a bookkeeper in their country of origin and is now a nursing aide here in the United States. The second category was that they had an increase in occupational prestige. They had five or more points higher in prestige. So moving from an administrative service manager to a computer scientist after migrating. And the last category was that they had a decrease in prestige. So this is five or more points lower. So this is somebody who moved, who was a post- secondary teacher and is now a janitor. This five-point cutoff range I did, I based that on the distribution of this difference score. And I just wanted to make sure that I had enough people in each of these categories to actually run my analysis well. But I was concerned a little bit about whether this five-point range was biasing some of my results. So I redid my analyses looking at a zero-point, two-point and ten-point cutoff range. And the results were pretty consistent. So I think that the results don't seem to be very, very sensitive to where I make this cutoff. So here's the breakdown of the different occupational prestige categories in the in the sample. The highest percentage of men and women actually experienced a decrease in prestige. This is down here at the bottom. And the extent to which this is true is actually quite striking. So 55 percent of the women and 42 percent of the men worked in jobs in the United States are actually lower in prestige than the jobs that they held in the previous in their countries of origin. The next highest percentage was those who had no change. 36 percent of the men and 28 percent of the women. And there were a good number of people who experienced an increase. So about 20 percent of men and women experienced an increase in prestige after migrating. The second measure was educational match. So while the prestige score compared an immigrant's previous work history to his current work history, educational match compared an immigrant's education to that of a U.S. born non-Hispanic white who had the same job. So for each respondent I compared his educational attainment to the modal educational attainment of non-Hispanic U.S. born whites who held the same occupation. So for example, if an immigrant worked as a carpenter here in the United States, I compared his educational attainment to all U.S. born non-Hispanic white carpenters. And I again created three categories. The first was the same education. So going back to this carpenter example, the modal education for U.S. born white carpenters was 12 years. So if an immigrant also had 12 years of education, they were coded in this category. The second group was those who were undereducated. So they had lower education. So this is being immigrant with nine years of education. And the last group was if they were overeducated. So this is an immigrant with 15 years versus the 12 years for the white comparison group. The way these categories sort of work out in my mind, at least when I created this, was that those who were overeducated, so this one here at the bottom, who had more education than the U.S. born whites, this would represent a downward mobility shift. Whereas those who were undereducated, I thought would represent sort of an upward mobility shift. And we'll talk about this later in the discussion, but this actually probably is not the case for the undereducated group. This might be capturing something else, but at least, you know, to give you a little bit of reference, that's how you can think about these categories for the different mobility directions. And so here's the breakdown. Again, we see that the highest percentage of those was of those who experienced who were overeducated for their position. So in my in my head, I thought this is people who were experienced downward mobility, 41 percent of men and 46 percent of women. The next highest percentage was those who were overeducated, 40 percent and 33 percent of men. And there were, again, a sizable number of people who were equivalent to whites in their education. Okay, so now that I reviewed the characteristics of the sample, I'd like to consider how some of these mobility categories are related to their depression status. So these are the rates of depression, their age adjusted to US born to the US born Asian age distribution for occupational prestige separated by men and women. And we see that for the men here, there isn't that much difference. The depression rate across the three categories of the prestige measure vary between 1 and 3 percent. But for women, we see a much more variation. So the women who sort of stayed the same in prestige have the lowest disability prevalence. And those experienced both an increase and a decrease have around 7 percent disability of depression prevalence. Here's the same bivariate tabs, but by educational match. And again, we don't see very much distinction across the groups for the men. For the women, we see a bit more. Those who have the same education have the lowest disability rates or depression prevalence followed by those were overeducated and those who were undereducated have the highest disability. So to test some of these patterns, I just conducted two logistic regressions that examined the association between depression and the different occupational mobility measures controlling for these covariates here. I had a set of demographic characteristics, a set of migration related factors, and a set of work and educational characteristics. And then my model, I ran two different models. This is the first one. It just looked at everybody together. Men and women together. And it compared those with the prestige increase or prestige decrease to those who stayed the same. And so here are the results of this model. I just have the results. I just have the odds ratios for the different mobility categories up there. I controlled for all of this. So we see that both those with the prestige increase and decrease have a higher odds for reporting depression than the reference group, which is those with no change. Those with the prestige decrease had a significantly higher odds. And I just graph the predicted probabilities to make the comparisons a little bit easier to see. So this is a reference group here in blue, which is the people who didn't change in their prestige. And they have the lowest. And it gets sequentially higher with the prestige decrease having the highest predicted prevalence of depression. And here's the same model except for the educational match measure. And both of the those who were overeducated and under educated had higher odds, but this didn't reach significance. So when I look at the predicted depression rates, we see sort of a similar pattern, but it's a lot weaker. The differences across the three groups isn't as distinct. So the second model I did looked at the interaction between gender and the different mobility categories. So there was individual indicators for men with a prestige increase, men with a prestige decrease and so on. The reference category was men with no change. And then here are the model results. And if we look first at the men, which is at this top two here, so everybody's being compared here to men with no change in prestige. So if we look at them within the men here, there's no significant differences across the prestige categories. If we look at the women though, we see a different story where those with a prestige increase and a decrease had significantly higher odds for this depression than the reference group. And again, here's the predicted probabilities just to see this in graphical form. This group here outlined in black is a reference group. And we see that the two groups that have significantly higher predicted disability are women with a prestige increase and those with a visual increase. And here's the results of the same model, but this time with educational match. And we see really similar things again where there's no differences among the men. But among the women, all of them have significantly higher odds in the reference group, but those who are undereducated and those who are overeducated seem to have the highest, which is illustrated again in this in this graph of the predicted depression rate. So I conducted several sensitivity analysis to make sure that my results were consistent. The first set that I conducted, I was concerned about this low prevalence of depression. And I was because I had several covariates in my model, and I was concerned that with this low prevalence of depression that this could be sort of messing up my results somewhat. So I conducted several models to make sure that my results were robust. First, I conducted a reduced model where I only included age and education into the models. The second model I looked at, I relaxed the definition of depression. So the scale that I used is for clinical depression and has a very strict algorithm as to who can eventually become coded as depressed. So I relaxed that somewhat and this brought up my prevalence of depression to between 10 and 11%, which is somewhat reflects the national trends a little bit better. And the last model I did use this waiting adjustment command that sort of controls, corrects the bias estimate if you have a very, very rare outcome. And all three of these models actually produce very consistent results. So sort of given these sensitivity analysis plus the bivariate trends, I feel pretty confident that these results are strong. The second sensitivity analysis I did is I looked at the role of income. And income was a little bit of an interesting variable because it's very highly missing in this sample. So around 35% of the sample had missing income data. But what I did is I conducted an analysis on a subset of the sample who had complete income data and I controlled for the effective income. And actually my estimates became stronger. So what this suggests to me is that this supports my idea that occupational ability sort of has an effect on depression apart from pathways related to changing income. Okay, so what can we take away from these results? Well, first downward mobility as measured by both the decline in occupational prestige and being over educated for one's position was associated with higher depression. And this is especially true for my first measure, their prestige measure. So earlier I had suggested that maybe things like job environment fit and aspirational discrepancies could sort of be these psychosocial issues that might be driving this relationship. And I don't have the data, unfortunately, to test this pathway directly. But I do think my findings are sort of promising and maybe give some support in establishing these ideas. Upward mobility was also associated with higher depression. But as I kind of hinted at earlier, I don't think the same things were happening between my two measures. For the prestige measure, when I took a closer look at the kinds of jobs that these people actually had in the United States, they were primarily concentrated in these sort of white collar professional positions, so leading me to believe that this did sort of represent an upward trend in the occupational status hierarchy. So in this way, it seems like those who experienced an increase in prestige did have these sort of higher status jobs and they could have had to contend with a lot of barriers to get where they were, which might have explained their higher rates of depression. But for those who were undereducated, I don't think this tracks onto the same idea because when I looked at the specific kind of jobs that those who were undereducated had, they were all concentrated in sort of manual labor and low-skilled work. So it seems to me that what this undereducated category is actually capturing is differences in educational status between immigrants and US-born whites who hold low-skilled jobs. So a US-born white worker who works in a low-skilled job might be more likely to have a high school education versus an immigrant who works in that same job. So what could have been happening is that job characteristics themselves could have impacted the higher rates of depression that we saw with this category. So, and I also didn't find any association between occupational mobility and men, which was contrary to my hypothesis. I think there's some very general reasons why this could have been the case. First, it's possible the benefits of migration could have outweighed any thoughts about their current employment situation. So we know that these are long-term migrants. They got their green card, so they likely intend to stay here in the United States. So it's very possible that they could have sort of accepted a lower status position in the hopes that their children or their grandchildren would fare better. Also, this, remember, was a sample with relatively short duration in the United States. And migration researchers who've studied occupational mobility have actually found that there's a trend where they're in the beginning, there's a downward mobility trend, but that's followed by sort of an uptick in occupational mobility. So all this to say that the employment trajectories might not have been established yet. And finally, there are just lower rates of depression for men overall. So the lack of variance across the categories could have probably contributed to the null findings. So while I didn't find any significant associations between occupational ability and men, we did find some interesting stories with the women. And it's likely that some very specific gender-related factors could have been intersecting with these issues. The gender roles that sort of inform my hypothesis are very traditional. The ideas of the male as the breadwomener, the winner, the wife, is supplemental to the household. But their migration scholars have sort of detailed the very complex relationship within households after migration. And they talked a lot about how gender roles change and their dynamic. And it could very well be that the intersection between gender roles work responsibilities and the migration dynamic could have compounded any sort of employment-related stress among women, which resulted in kind of the very stark differences that we saw compared to men. So finally, there were some limitations with this study, but I see as areas for future research. The first is that this data was cross-sectional, so we don't know whether employment preceded depression or the other way around. Fortunately, the NIS was designed as a longitudinal study. So these participants were followed up in 2008. And the second wave of data is supposed to be released sometime this year. So I'd like to follow up this analysis with a longitudinal study that might be able to get at this causality issue a little bit better. Also, I proposed several mechanisms, things like stressors, job characteristics, but I wasn't really able to test any of them. So in the future, I don't know if I'll be able to test it in this data set, but in the future I'd be able I'd like to look at sort of these mediating pathways a little bit more carefully. And finally, I think the most interesting finding that I had was that women with upward occupation mobility had higher depression. So in the future, I'd like to consider gender explorations more specifically in my work. So I kind of alluded to some potential friction between work and domestic roles for these women. But we also know that immigrant households are very unique to some non-immigrant households. So for example, we know that a lot of women leave their children behind when they migrate or they live with large extended families or that depending on who the visa sponsor is, whether it's the husband or the wife that introduces a new power dynamic that can sort of upend a lot of gender roles. So I'd like to look at these sort of immigrant household formations a little bit more closely, especially among these higher status women. So thank you. Yeah. So one of the biggest impacts I think on life when we migrate is the living in social network that we're not even trying to establish a new one. Right. And in my mind, that probably explains some of the gender issues because women tend to have stronger networks. Right. And that brings two topics that I'd like you to comment on. One is if one were to look at the trends, I know you didn't do it on the street last time, but one of the things I would expect is as it becomes easier to electronic communication, email, Facebook, as this trend, this gap between men and women decreased because it's now easier to have a network that's global. The other topic is the measure was depression. And you said that your life that will change a little bit. But testing for social network, there is another WHO instrument in quality of life. There's also an average version that may have got into this particular issue of social network impact on quality of life. I think it was also developed by the mental health department. Yeah, the issue of social networks is a really interesting one and one that I'd like to explore more fully because I've given this talk a couple of times. And one thing that people bring up that's kind of related to social networks is that I look at, I suggest that men and women have these different patterns. But one thing that's come up is people have said, you can't separate the men from the women. What's going on with the men is probably affecting the women in the same way. So you should maybe look at what's going on within couples and looking at matching of occupational ability within couples. But I think to speak specifically about social networks, I know that the NIS has some measures about how often you keep in touch with different people. And I haven't taken a look at that. But I think that would be sort of an interesting way to think about it. I guess I'm trying to think about how I can relate that more closely with sort of their employment outcomes also. And I guess it's hard because it affects both their depression status as well as sort of their employment status. But I think, I mean, that being said, I do think that there are some valuable measures here in the NIS that I could definitely take a look at to kind of get at what their social networks are, both what they have, what sort of contact they have with the people in the country of origin, as well as sort of the new social contacts that they're establishing here in the United States. So I'll have to say, I think that's a wonderful suggestion. I'd be glad to look at it further. Your comment about the quality of life measure, I did look at self-rated health as well as depression, and I didn't see anything with self-rated health. I'm not to the same degree that I saw with depression. So I think that some of these pathways might be specific to mental health, specific to psychosocial stressors that impact mental health. So I think if we're thinking about overall wellness and quality of life, can we generalize it to that degree? I don't know, but it does seem like there's something going on here with mental health. So when you start by giving an anthem yet about the taxi driver, what might have a lot to do with you from somewhere else. So the presumption I had before you kind of said that that's downward mobility that we want to protect against is that there are some income gains in immigration in general so that there's not benefit. So even if a lawyer in some country is a lawyer and has prestige, they're still making more money as a taxi driver in New York City despite the fact that the prestige is lower. Right, right. So does that, in terms of the income result that you found, you said controlling for it, does that imply that income reduces your, more income reduces the risk of depression, but that it doesn't kind of explain this? Yeah, that income doesn't explain away the associations between the different mobility categories. And I do, what's interesting about the NAS again is that I have their pre-migration income as well. So I did try to do a difference measure looking at the difference in income right before they migrated to their current US income. It's a very messy measure, but I actually, I found that difference didn't explain away this either. So I think that it's something unique to their occupational status and sort of the roles that are encompassed in work that's separate from just the jump in material resources that they might have after migrating, yeah. All right, moving into mobile. So today we're very lucky to have Dr. Imran Khan here from the International Vaccine Institute, also known as IVI, which is based in Seoul, South Korea. Dr. Khan joined IVI in 2008 as a research scientist and has been working on high-poly vaccine production in Nepal and Pakistan. Khan received his Master of Science degrees in Epidemiology and Biostatistics, as well as his medical degree in Pakistan, and he received his PhD in International Health from the Johns Hopkins Bloomberg School of Public Health. We were in the same cohort at Johns Hopkins University, so he also received somewhat of an honorary degree in Food Preparation and Survivorship because he would oftentimes call our cohort to his home, pack up some food, and then we could survive the strenuous program for another day. But today we are here to hear about his research interest and that is vaccines against infectious diseases. So without further ado, please join me in welcoming Dr. Khan. Thank you very much, Brandon. I want to use the mic, so that... The mic, please. Yeah, it's more attentive. Is it working now? Yeah. Okay. It's a pleasure to be here, and two ways. One, I'm seeing Brandon after two years. And secondly, to share my work and our work that we have been doing for the past 10 years. What I'm going to do today is that I'll briefly describe the impact of immunization on infectious disease globally, and then introduce you to the institute that I am working with, International Vaccine Institute, and how International Vaccine Institute is trying to reduce the gap of access for those people who really need the vaccines that are available in the market for a long time. And then I'll use a case study of TIFIED fever program that exists at IVI to tell you on the different areas that you work on. I just want to start with an acknowledgement to the people whose contribution is in the presentation today that I'll be talking today. This starts from a health worker and a child getting the vaccine in developing countries to our funders, which is the government of Korea, Swedish government, and Bill and Melinda Gates Foundation. Without their support, it would have not been possible for me to stand here and present the work. Just to start with the concept of why we have vaccines, it goes back to the concept of immunity. The concept of immunity is so complex that we still are trying to understand it. It's not possible for us to have the complete understanding, but to make it very simple, it's a mechanism of the body through which either it tolerates the intrinsic organs or the system of the body and also identifies if there's an external factor that could damage the body and protects the body against some external factors. Two ways the body does it. It is one is active or passive. Through active, the body internally recognizes the external factor and then produces the stimulus, humoral or cellular mechanism to protect. Or it could be given the same, mostly these are immunoglobulins which are the immunity factors, immune factors, which are given from outside to make the body prepared to protection against the disease. A vaccine follows the same concepts. It's an immunological substance used for active immunization by introducing to the body a live, modified, attenuated, killed or inactive infectious organism or its toxin. But I would like to reiterate here that not all vaccines are perfect. There are vaccines that the person may be vaccinated but it does not mean complete protection from the disease. Why are vaccines important? We repeatedly say that this is the most cost effective intervention in combating disease and has really resulted in a lot of reduction in the suffering of the human population. And one picture that you may, if you see on the left, not many of you have seen the actual cases because it was only possible because of the use of the vaccines that we got rid of this disease from the whole world. So smallpox is no more existent in this world. It also increased productivity and thereby it may indirectly affect the poverty which is one of the millennium-developed goals. The history of vaccination goes back to the Chinese what the documents that we find are from early 16th century where a concept of viralation was used in China by the Chinese practitioners whereby they would use the smallpox from the legion of the smallpox and put it into the human body who are healthy individuals and they found that it protects against smallpox. What we have achieved so far with the vaccines is that we don't have smallpox anymore. We have controlled almost 99% of poliomyelitis globally. Measles are eliminated in most parts of the world. Other diseases such as diphtheria, protrusus tetanus, rubella and meningitis are controlled in some parts of the countries and we have developed countries specifically and some parts of developing countries, the burden has been reduced and we also know that for some diseases such as hepatitis D, meningitis C and varicella and nemococcal disease in developing countries, these have been controlled. If you look at the trends of child mortality from 1970 where it was 17 million per year to 2007 where it reduced to 9 million per year that has been a significant decline but yet we are not there and the target that the global community, global public health community has given is that by 2015 we would reduce it to 4.3 million per year. I don't think that we will get there but we still are in a declining trend which gives some hope for us that one day we would be able to control. Why vaccines are important that if you look at the trends or the reasons for global child mortality, most of these diseases such as diarrhea, pneumonia, malaria, measles are vaccine preventable. So thereby if vaccines are used and if we have increased the access of vaccines to the population who need it, what we be able to do to achieve is that we will have a significant decline in the under fire child mortality. After the smallpox eradication back in 1974, it was realized that there are certain vaccines that are available and we should have an increased access to the population for these vaccines and the expanded program on immunization started back in 1974. And you can see that initially there was a trend of increased coverage, but then now it has reached a plateau and there's no country where vaccination coverage is 100%. Even in developed countries, vaccination coverage is not 100%. So that shows that the decline or the access to increased access in the vaccines initially has now been facing some problems. One of the reasons that we vaccinologists usually say is that vaccines are their enemies themselves. What happens over time is that there's disease that is death associated to that disease and there is fear. And when people see that they are dying because of certain disease, there is a demand for the vaccine. With increased access to the vaccines, the disease gradually disappears and we do not see the disease anymore. So we are not scared of the disease anymore. So if you go and tell them that this is the disease for that vaccine and they say what, which vaccine? So for as an example, I would like to ask you a question. How many of you have heard about typhoid? Oh, many, your childless. But if you go out and talk to people, they don't know if there is typhoid. And interestingly, when we talk to public health community, the practitioners in developing country where there's a lot of typhoid, not many people know there is a vaccine for typhoid. So that's where we have to work. And the person who is really, really influential today in the global health community, Bill Gates, he was younger here. So he issued a statement and one of the areas that Bill Gates Foundation, Gates Foundation has been very much interested in is to support vaccination and vaccination programs. He said immunization remains one of the best buys in health. Nothing on the planet saves children's lives more effectively and inexpensively than vaccines. Now this is the global vaccine pipeline. The bigger the circle, the bigger the burden of the disease. And the first green line is where vaccines are available to the people. The yellowish or orangeish is the underutilized vaccines. These vaccines have been there for many years, but they are not used. And then there are areas where we don't even have a vaccine. So it gives us a huge challenge as public health practitioners and experts that we need to combat diseases by effective control. And as Gates Foundation said, Bill Gates said, that it could be done effectively by use of the vaccines. Understanding this gap and the benefit of vaccines in the International Public Health, International Vaccine Institute, where I belong to, was initiated as a UNDP initiative in 1996. This is the first international organization in Korea. And 32 countries are signatories, including WHO, that means that they agree to the mission and vision of International Vaccine Institute. Our focus is on vaccine development and research. And we have field programs in 30 countries, Asia, Africa, Latin America. You may notice that we are not working in developed countries, which this does not include Americas and Europe. We have lab facilities that are based at IVI, which is in Seoul. And our mission is to combat infectious disease through innovations in vaccine design, development and introduction, while addressing the needs of people in developing countries. We are focusing on the diseases, such as enteric and viral diseases, and on dengue. These are our area, focus areas, but that does not mean that in future, we may not be working on other diseases. Wherever we find the need, we will start working on those. This is a graphic presentation of the places where we work. You see, we are present in Africa. We are present in Latin America and Asia. There are 146 staff. We are not that big. We are not that old. We are new. There are 42 international staff. There are 86 scientists. And we have a board of trustees that comprise of 13 people. And most of these are coming from high repute scientists, including representatives from the government that are funding us. And we have also a scientific advisory group that directs our scientific vision towards achieving our mission and goals. We have been in the past focusing on diseases, such as on enteric cholera, rotavirus, shegelosis, taffyde and para-taffyde fever. On respiratory illnesses, our work has been on pneumococcal pneumonia, hemophilic influenza, tuberculosis, flaviviruses, such as Japanese enkelephates and dengue. Our scope of work includes epidemiology, clinical trials, demonstration projects, economics, social behavioral studies, applied biases and disaster response. Our focus is to reduce the gap between rich and poor. How do we do that? First, we want to try to have an impact in the near future. The way we do is that we try to identify a problem, mostly in developing countries, and then we see whether there's an intervention available. If that intervention is a vaccine, we try to increase the access and work with the governments, with the academia in that country, and to increase the access to that particular vaccine intervention. If there is a vaccine available for our disease, but it is not, there are certain limitations with the vaccine, we try to improve the vaccine in terms of it may not require cold chain, it is a single dose, it may not be injectable. So this is the area that we work on. So if there is a vaccine available, which has limitations, we try to improve the characteristics of that vaccine. And if there is no vaccine, if there is a disease, there is a problem, the burden is high in developing countries, but there is no vaccine available. So our scientists in the lab in Korea are working on trying to find antigens which could be potentially used for vaccine in the future. We also provide technical assistance. We conduct, we have a vaccinology course every year. It is held in May. And where we invite scientists from all over the world and we talk to them about how vaccinology can have an impact and how they can use the knowledge of vaccinology to control infectious disease in their respective areas. Some of the things that we have achieved in the past 10 years, 10 or 11 years, there is a vaccine for cholera now before, there used to be a vaccine for cholera, but it was two dose and it needed a buffer. So we, our scientists improved the vaccine and now it's WTO pre-qualified. It does not need a buffer, it's still two dose. We are working to find out if we can use it in a single dose. So for any vaccine that can be used in the developing world, WTO pre-qualification is kind of a standard. And, excuse me, so what it means is that now with the WTO pre-qualification, cholera vaccine, you must all know about what happened in Haiti two years ago. And the reason that the vaccine was not purchased and used was that it was not WTO pre-qualified. So without efforts, now we have a pre-qualified vaccine for cholera. There is a project going on on cholera vaccination, but having said that, I'll say that this field of vaccinology is such a challenge that although we have the vaccine pre-qualified, but we only have one manufacturer who is pre-qualified, so their production capacity is not as much so that they can supply even Haiti, which is not that big a country. That manufacturer is not able to supply whatever the demand is. So that's my second bullet. We are trying to, by increasing access, I mean that we want to have multiple producers all over the world. So that, number one, the manufacturer does not dictate their terms and conditions. Number two, we have more manufacturers and there are more vaccines available for use. And then we are also working with the governments on the disease that we are working so that we can build a policy and we can change their mindset that there are no vaccines. These are not controlled, these diseases cannot be controlled by the vaccine. And then we are also working on the way the vaccines can be given. One is the sublingual and we have a project that we are working on to try to see that how effectively and efficiently this method of vaccination can be worked out. Then we are also working on adjuvants and we have our scientists in the lab have found an adjuvant which really increases the immune response to the vaccine. As an example, I would like to talk about the Ta-fied Fever Program. My work has been mainly focused on Ta-fied Fever. It's a bacteria infection. That is very, the contamination sources, food and water. It results with high grade, constipation may have constipation, diarrhea and there are many clinical symptoms. But it starts as fever. So the challenging part of this disease is that by the time it is diagnosed, it has already started into going to the complication phase. And one of the major complications is intestinal perforation. And then in areas you can imagine where this disease is common, intestinal perforation is an acute emergency and healthcare sector is not really equipped to handle and it may result in death. The literature estimates that there are 21 million cases all over the world. There are two vaccines available in the world that are marketed and licensed. But there are many barriers for these vaccines to be available for the people where the disease is. So as our Ta-fied Fever vaccine program at IVI, what we are looking at, is that we want to accelerate the access to Ta-fied vaccines in the developing countries or in the endemic areas where Ta-fied is. And then we also want to pave the way for this introduction so that it can be introduced at a large scale and the government takes up the vaccine in their public health programs. And since the available vaccines have their limitations, we are also working on some innovative ways of coming up with a vaccine which is better than the existing vaccines. If you look at the disease burden, you see this is the map from the WTO that was published in 2004. We see that most of the disease is common. The gray shows where the disease is more common. The disease is mostly in South and Southeast Asia. 99% of the Ta-fied is in that area. If you compare Ta-fied with other diseases, which are priority, you see that the morbidity based on the two yellow bars are the first estimate is from the old estimate that was published in 1984. And the other one is from 2004. So although we don't know much about it, but since it is common in the area where most of the population lives, I mean India is one billion, then if you include Pakistan, Nepal, Bangladesh and Indonesia, it's another billion. So that's why it contributes a lot to the global burden of the disease. So comparing to other diseases which have higher priority and on the radar scale and all of us talk about let's say HPV or other diseases, Ta-fied does come up to that level, but it's not in the radar screen. That's why back in 2000, in 1999, we got a grant from Bill and Melinda Gates Foundation. So our project focused on trying to bring the diseases that are common in the developing world but are not being noticed in the places where the funding is available. So we used a multi-sectoral approach of trying to identify the burden and then to advocate at different levels so that these diseases are highlighted in the international community. We used disease burden studies. We did meta-analysis for different countries and then we did feasibility studies, try to assess whether these vaccination is possible. We did cost-offinness studies that would also help us to find out if Ta-fied vaccines are cost-effective or color vaccines are cost-effective. And then we also assessed the demand, whether there is a demand for these vaccines in the decision-makers, in the population, in parents. So these studies are conducted in Bangladesh, China, India, Indonesia, Pakistan, Thailand, and Vietnam. I'm not going to present all the data but what I want to present here is one of the results from our study where we saw that how common is the disease. So that was our first question. If you are saying that there is disease in these areas, if it is really common, because before the disease was the burden estimates were coming from some studies at small scale. So IVI came up with a multi-country approach of showing that in countries, how much is the disease there? And we saw that out of these five countries that the disease was more common in Pakistan, Calcutta, and Indonesia. And one of the reasons, one of the major contribution of our research here was that prior to our study, it was considered that this disease is not common in less than five years, but if you see at the red bars, you can see that it is very much high and even in Pakistan it was much higher than five to 16 years of children. Another problem with this disease that there is a lot of antimicrobial resistance and if the person who is sick, even if they are getting antibiotics and the bug is resistant to that antibiotic, is not going to work and that patient may go into complication. And these bars show that how much of resistance is there against salmonella typhi for the commonly used antibiotics. And in Karachi, even the antibiotic resistance reached up to 70% to nalytic sick acid. So the resistance is really high. Similarly, it was there everywhere, even in India and Vietnam. We also tried to assess that if the perception of the people, the perceived prevalence correlates with the actual prevalence of the disease. And you can see there is a high correlation of perceived prevalence with the actual incidence of the disease in these countries. So in the countries where the disease was rare, people did not think that typhoid is a problem. We did cost-affiliate studies to find out that how much does it cost? It also helps us, as I mentioned earlier, to find out that whether vaccine would cost more or the disease causes more. And you can see that the numbers are very high. And for the hospitalization, in studies such as China, 40% of the hospitalization rate was because of typhoid, 2% in India, 20% in Indonesia, 10% in Karachi, and 28% in Vietnam. And it ranged from $432 in Indonesia to $129 in Calcutta, India. And the blue portion of the bar shows out-of-pocket. So it means that people are paying out-of-pocket because the insurance system does not exist in these countries. Whereas if you look at the cost-of-culture confirmed illness, you can see that China was much higher, and then it was Indonesia, and then with Karachi, and then in Vietnam, and then Karachi. So between $15, US dollars, and $132, it costs a simple blood-culture confirmed case of typhoid fever. Our results, based on our research, resulted into the modified position paper on typhoid. So the World Health Organization publishes position paper on different diseases and their vaccines. And it was highlighted for the first time that the World Health Organization recommended that vaccines should be used in higher endemic areas. Now, there were some questions, there are two vaccines available in the market at that time when this project started. What is that old, killed wholesale vaccine, which the side effects were much higher, the rates of adverse events associated with this vaccine was much higher, so it was not very commonly used. There were two other vaccines. One was injectable vaccine, VI polysaccharide, and there was oral TY21 live attenuated vaccine. The reason International Vaccine Institute decided to choose VI vaccine was that it was a single dose. It was safe and effective. It was not protected at that time by patent. It was not patented, so it was easy for us to transfer the technology to a developing country manufacturer. But there were some other issues that whether this vaccine will work in less than five years, all the studies that was done on this vaccine were on five years and older. So there was no data on less than five years. And also that there's a concept of herd protection that if more people are vaccinated in the community, so whether all those who are not vaccinated in that community will be protected. So we want you to address this question also in our study. I'm going to talk about the project that we started in 2000 in Pakistan on the demonstration project of VI vaccine. Our objective for this research was to assess the effectiveness of VI polysaccharide vaccine when administered under realistic public health conditions in a cluster randomized, effective in this trial in low socioeconomic settlements of Karachi, Pakistan. We started with an initial census and then there was a one year of surveillance. During the surveillance, we did social behavioral studies, the results which I presented earlier and we also did a case control study to find out the risk factors for typhoid fever. There was a pre-vaccination census where we updated the information on our database. And then later on we vaccinated and after vaccination we had a post-vaccination surveillance where we were tracking all those children who were getting typhoid fever. The blood culture positive was our outcome. We also had post-vaccination social behavioral studies and we also did an immunogenesis study. And then we closed out the census and then we analyzed our data. So what our surveillance system was that we set up health centers in the target population. We were also working with the private practitioners. So the children, any child that is between two and 16 that would come with a history of your to be identified, they will go to the study clinic, they'll be attended by a physician, blood will be drawn if they were eligible to be enrolled in the study. And then the treatment will be started at the same time the physician will be waiting for the blood results. If the child was blood culture positive, the child will be invited for a follow-up at a later stage and the physician will again assess if the child was blood culture positive. The, based on these culture sensitivity results that either the treatment regimen would be changed and will stay the same. This is a geographic picture of the study site in Karachi, Pakistan. There were three sites that we included. We had 120 clusters, 60 clusters were included in each arm. As I mentioned, two to 16-year-old children included and if they were considered to participate, had no fever and were not pregnant. The vaccine were VI polysaccharide vaccine and the control vaccine was hepatitis A vaccine. I will just briefly present here the results that you see that our total protection for the vaccine were 35% and it is not statistically significant, which was a surprise to us. So what we did was that we assessed whether it works in different age groups and we found out that our results were consistent with the studies done earlier that this vaccine protects against typhoid fever in children five to 15 years but it does not work well in less than two to five, in less than five years. So now what are the implications of this? What were the implications of these results? That we are vaccine may work, but it will only work number one in five years and above and number two, it may not give protection to those who are less than five years because unless you vaccinate everybody in the population. But since it was protecting the school children, so it may make sense to vaccinate the school-age children because they're also at the high risk and it's easier to vaccinate the children. From here, we took another step and we got another project which is called VI vaccines for Asia. The goal of this vaccines was that based on whatever we had learned from our first project, we wanted to make to ensure that there is a cost computer supply of VI polysaccharide vaccine and then we wanted to accelerate the use of this existing vaccine because this is not a good vaccine, but this is still available. So we wanted to advocate for the use of this vaccine in the current public health programs. And then we also wanted to make an investment case for the global community because financing the major issue in the increasing access for the vaccines and developing work. The countries are always stressed with their health budget and then vaccines if they are not available in the existing program, the purchase and the administration of the vaccine may pose other financial impacts on the budget of the governments. So we wanted to use this investment case to advocate at the international level, at the local level for their policy so that there's a demand for this vaccine and those who could, for example, Gavi can support the developing countries for the use of the vaccine. And also we wanted to ensure that this vaccine is again pre-qualified so that it can be used. So the limitation that we realized in the previous project were that the vaccine was not pre-qualified by WHO and it was only less than for two years and above. And the current direction strategy was not feasible in the API schedule because of the age restriction. All the vaccines that are even in API are less than two years and new implementation platform are required and TIFI vaccine was not Gavi supported. And then we wanted to make an influence on the policy so that we can negotiate with the governments and the international donors so that they can support this vaccine. And that's what we did. So for the vaccine, we are also working on a V-I conjugate vaccine in the current project and we want to increase the global access so that there are more producers and there are more vaccines in the world. And then for the existing vaccine, we worked on a pilot introduction program in Nepal and Pakistan so that we can show the evidence that the vaccine is acceptable and the coverage is high. We also tested that if you can use a cross-subsidization model to see if the vaccine can be, financing of vaccine is possible within each country. And at the WHO, we had some policy initiative where we had a person who would be talking to the WHO representative over the vaccine and see us. How am I doing time? Five minutes? Okay, I'll be quick. So this project focused mostly on the preparation phase where we had advocacy meetings, social mobilization activities, vaccine fund establishment and social mobilization activities followed where we also had the vaccination phase and we also collected the fund during this time. And then post-vaccination with that feasibility assessment, impact assessment, impact assessment and economic assessment. So what this cross-subsidization, I just want to take a minute to describe you what this model is. So what International Vaccine Institute did this, we supported the vaccine, many vaccine manufacturers for the purchase of vaccine and the vaccine was given to the vaccine administrator which in one case was the Ministry of Health Department. We also supported the vaccination cost. It was given to schools. Pay, we divided the schools into two categories. Those vaccines, the schools who were from well-off families, they would pay for the vaccine and those who could not afford, they would be, they would get it for free. So for those where we sold the vaccine, we will have a revenue generated. This revenue will be used by a revolving fund and this revolving fund will be supervised by a technical advisory group. They will in the next cycle, supply the vaccine to the vaccine, give the cost and supply the vaccine to the vaccine administrator. Similarly also support the vaccination cost and this vaccine, this will revolve in the cycle. And again, it will continue. And the cross-ubstitiation model in Pakistan was that in the schools, as I mentioned, some schools which could afford with purchase of vaccine, those could not afford will get the free vaccine. In Nepal, what we tested was that it was in the tourism sector, all those people who were involved in the tourism industry like tourism workers, they would purchase the vaccine and the revenue will come and then it will go to the free vaccine sale. Although we understand that vaccines are available but there are certain challenges at the population level, people may not know whether there is a vaccine. If they know there is a vaccine, they may not understand the benefits. If they understand the benefits, sometimes they are afraid of the adverse events. So that's why we realized that there is a need for us to understand our population more. We did a formative research, there were different phases where we went to the population, we interviewed them in different sectors of the population and we talked to them about the disease, we talked to them about the vaccine, we talked to them if you would receive vaccine, how would you receive it? We talked to them if, what would be the questions they would, you would like to know about the vaccine and its effects. So our key findings were that people knew about Tafat fever, everybody knew about Tafat fever, but they did not know how it can be prevented. They had a vague idea, some would say maybe washing hands, some would say drinking safe water, something like that, but they did not know what, nobody mentioned vaccine. And if they would, if you would tell them that if there is a vaccine, they were willing to take the vaccine. So that was something positive for us. So we use all this information of us, our findings and then we made it into information communication campaign. So we thought that it will be difficult for us just to go and offer the vaccine and give the vaccine. Then we may not have a good coverage. So what we did that our staff went and visited like four times to each, because this was a school-based campaign, to the schools and they tried to introduce the project, they tried to tell about the benefits, they met the parents, they met the children. So our key findings are that, I'm just summarizing here, that the Tafeid vaccine is safe, there are no major adverse events related to the vaccine. And then there is a demand, people want the vaccine, but they have concerns. Unless you address their concerns, you may not get a good coverage. As I show here, although in Nepal, the routine vaccination coverage is around 90% but for us it was 60%. So when we showed 60% to the government, they were like shocked that how can it be 60%? But the reason was that, whenever you go with a new vaccine in the field, they always think this is new and they are always concerned that, are we like guinea pigs, are you testing it on us? So if you don't inform them properly, you may not achieve good coverage. What we learned in this vaccination campaign is that, vaccination campaigns themselves help in social mobilization. They also inform people. People have more confidence in the intervention and the vaccination coverage increased dramatically in Karachi from 30% to 60% and it was 20% in Nepal. What we, the very innovative model of revenue generation I showed you, we found out that it's not possible in these poor settings to generate revenue internally. So we are looking forward for Gary to support this immunization program. My conclusion maybe that immunization is one of the most important public health intervention history after safe drinking water. So we should not just say that vaccine, vaccine, vaccine. Vaccine work and there are vaccines that work differently. Some vaccine work in one area much better but they do not work in other areas. Rotavirus for example is an example. There are other other examples as well. So we do not have to promote vaccine only. What we have to do is that we have to say that, okay, vaccine works but you have to continue work on other interventions as well. And specifically it is very true to the bacteria or the entire like enteric diseases where water and drink and food is the source. Immunization has saved millions over the years and prevented hundreds of millions of cases of disease but I think there is a lot for us to do. As I showed you that we have not yet reached our goal that we set for ourselves in the millennium development. So we have to do more and there are a lot of challenges that we have to face. These challenges are from the target population up to the policymakers at national and international levels. I'd like to thank you here and I'll say that vaccines do not save lives but vaccination does. We as public health professionals, our job is that oh yeah, we can have a vaccine but if it is not reaching to the population it is never going to save lives. Thank you.