Discovery Matters | Ep81. Access in developing nations
Dodie you know that I grew up in what is now the Democratic Republic of Congo what was then zier so from a very early age I had a vaccination passport and now I work in this industry where access to vaccines and adquate healthc Care infrastructure matters a huge amount so in this episode we’ve got two really fascinating conversations from two parts of the patient Health Care workflow access and Diagnostics all right so access in developing nations is what matters today undiscovery [Music] matters medical schools in the US are rather expensive this is Dr Jerome Kim director general of the international vaccine Institute or ivi he’s had the most incredible journey into infectious diseases so there was a program because of the cold war that existed where if the US government would pay for your uh medical school and give you a stipend and pay for your books if you would pay back one year for every year of that they paid luckily the Air Force had a program where you didn’t have to go directly into the air force so I did my training at civilian uh institutions Duke University and um got a grant then got another Grant and finally I wrote to the Air Force and said hey can I stay uh and and finished my grant at Duke I’m you know now on the faculty Etc and I got this email back you managed to slip below the radar for too long I’m going to send you to work at this Walter Reed place they need a doctor who’s interested in doing HIV vaccine research and that’s how I ended up working for the Army so I was Air Force working for the Army I worked uh with Bob Redfield who eventually became head of CDC and Debbie Burks who became the global AIDS coordinator and then the uh White House person for Co and did laboratory work and um saw patients in the vaccine clinic and eventually sent to Thailand to take care of the phase 3 trial for HIV vaccines because I helped work to set it up and it was having some trouble and they needed someone who understood it the vaccine was still and is still the only one to show protection against infection it was only 31% then I retired from the military and joined ivi and ivi works on a slightly different kind of vaccine so HIV vaccines we consider unincentivized it’s a huge problem uh it’s also the best funded of all the neglected diseases if you look at the funding for HIV TB or tuberculosis and malaria you have 90% of the funding for neglected infectious diseases Dr Kim works on that other 10% that’s what ivi works on and has been successful uh in taking vaccines from the laboratory through clinical testing approvals stockpiling uh and establishment of a post lure mechanism for purchase and distribution and um so ivi has a natural interest in in vaccines that we call unincentivized vaccines that no major Western pharmaceutical manufacturer wants to touch because the profits are not sufficient uh to justify the significant amount of research and development um investment that they would need to make um on the other hand with funding from The Gates Foundation or the welcome trust or others we can take vaccines forward with uh developing country vaccine manufacturers which you’re capable of manufacturing a highquality product at a level that passes the World Health Organization pre-qualification requirements and then get that vaccine used uh by countries around the world so that we have an impact on the disease we’re interested in now we’ll come back to the work of the Gates Foundation for the second interview of this episode Dr Kim just said 90% of all infectious disease funding goes to HIV tuberculosis and malaria even you said it I can’t really get over that uh to me that’s just an incredible number and how does that span out in terms of populations affected yeah it’s mind-blowing and it’s actually worse than you think because that 90% is actually funded by governments primarily and by some philanthropic organizations as you can imagine the United States doesn’t have a huge tuberculosis problem so it’s unlikely that a us-based vaccine company is going to invest a significant amount of money in testing and devel veloping a tuberculosis vaccine the last big company to be involved actually there are two kind of sad stories one is the um malaria vaccine that um GSK which is a major company and a great vaccine company developed for malaria the vaccine was efficacious at a level of about 50% um funding for it dried up and this is philanthropic funding largely dried up and the vaccine was stunk the World Health Organization did not want to recommend it or approve it and um so people were wondering should is this a vaccine that we should use and GSK was stuck with this vaccine that was efficacious that many people said would save hundreds of thousands of children’s lives every year and it wouldn’t move forward because there was no one who wanted to manufacture it a 50% effect is not going to be convincing unless you have appropriate levels of uh Effectiveness data that is real world evidence the vaccine actually does what it’s supposed to do and is costeffective and it took 3 years to do that so malaria vaccine was waiting in the wilderness um for 3 years you know hundreds of thousands of children died um but now it can be uh recommended and used and and it has been and and usage is picked up can this be characterized as a problem of market failure yes the this is exactly what it is the lack of a financial incentive is an issue but it’s also about the different experiences of infectious disease between the nations with the resources and those without the resources there are some vaccines for conditions that exist in high-income countries but for which no vaccines have yet been developed and and where there’s not a lot of big company interest in developing a vaccine last year there were significant number of cases of scarlet fever in the UK and also a significant increase in the number of of cases of very very severe stre coal skin infections they’re all caused by the same germ strepto cacal fitis and um in parts of the world that don’t have access to Good Health Care people get a case of of shower throat from uh group a strep then a few of them develop something called acute romatic fever and after that every single time they develop a a strep a infection they get a little worse case of this romatic destruction of the heart so that by the time they’re 20 to 30 they develop heart failure and die and you’d think well that doesn’t sound very common but in low and middle- inome countries 300,000 people a year die of this those of us who’ve been parents know that all you need is a series of group a strep infections running through a nursery and all of a sudden your child stays home from daycare and you have to take them into the doctor and you can’t take them back until they’ve been without a fever for 24 hours in the high inome Countryside it’s also a significant disease and it’s a significant disease from the the perspective of parents because of time lost from work of the visits to doctors it’s estimated that 50% of the prescriptions handed out by pediatricians are for group a and 50% of them are not being are not being prescribed are being misprescribing doll problem in the United States alone in terms of total cost to the um Health Care System we don’t have a vaccine we don’t have a major company working on it why the way they estimate risk and the way they think about risk and benefit is different so you know we’ve done an economic analysis that would suggest that a a strep a vaccine could potentially yield $4 billion doar per year to the company that develops the first one now is that enough for a vaccine company no because they want to know what the risk of failure is they want to know if there’s a risk of complications then it becomes a very different calculation when a company is thinking strongly about developing a new vaccine what they’re looking at is the 90% risk of failure against a 10% chance that they might make $4 billion for many of them that is not a risk they’d like to take what if we were to encounter a disease which did meet all the requirements to incentivize a company to make a vaccine so for example what if we thought about a large population in higher income countries uh being at risk and this disease were to have relatively High mortality rate and relatively High infectiousness remember that covid may be killed 2% which is not terribly dangerous something that kills 2% of 8 billion people kills an awful lot of people it’s the ability of the virus to spread through the community and then the number of people who get hospitalized and then the number of people who die and and so there’s a balance between those things in terms of what constitutes the greatest risk if you look at the thing that causes strep throat it kills 500,000 people so 300,000 from um rheumatic heart disease which doesn’t kill you right away then 200,000 from um other sorts of infections that group a St are involved in that’s a significant number it may actually be the number four number five greatest infectious disease killer among the different pathogens the Simplicity of developing a vaccine so if it looks like people who get the disease are protected for life after they get it like measles then developing a vaccine may be relatively simpler than a disease like HIV where you can be infected and then while you’re still infected get reinfected and reinfected again and then the viruses recombine and and outsmart the immune system at every step there are certain pathogens that are going to be more difficult finally there are diseases like chalera and typhoid and others that kill between 100 and 200,000 people a year often they they more often kill children than adults who um you know an adult living in Nepal may have been exposed multiple times or S successfully survived multiple episodes of typhoid because they got to treatment in time or because they didn’t have the severest manifestations of the disease on on the other hand a six-month-old who contracts it may have a very Rocky time and and may end up dying of of typhoid or dying of chalera so who makes those vaccines uh typically these are what we call developing country vaccine manufacturers but the power of the purse is going to play a role it certainly will a vaccine against a disease called Rona virus um which causes significant diarrhea um is available in the US it’s actually been available in the US since 2006 or 2007 and right after it was introduced the number of cases of Rota virus dropped almost to zero on the other hand 60% of the world’s children have not been vaccinated now this is 16 years after it was introduced in the United States 13 years after it was recommended and approved by the World Health Organization it’s just taken a long time for this vaccine to trickle down into low and middle- inome countries so the companies that make the vaccine sell the vaccine for between 70 and $150 a dose in the US and and slightly less in Europe but still at a a reasonable price in the developing world you can’t pay $100 a dose or $70 or even $50 a dose for vaccine and the the organization that purchases and distributes vaccine the two Gabby and UNICEF would go broke if they had to pay $50 a dose to vaccine they get the rotavirus vaccine for A110 cents a dose because there are two Indian manufacturers competing against each other and so these Indian manufacturers can make hundreds of millions of doses of wh approved highquality vaccines that prevent rotus infection great um but they don’t make a lot of money on it American GSK do make a profit on their rotavirus vaccine so they’ve recouped the R&D costs which were substantial what the Indian companies and other companies are doing is they’re saying well that proves that it’s possible now if we make a similar vaccine and we um start to to sell it to Gabi or UNICEF um we can sell it for much less and we can vaccinate far more people and that’s exactly what they do 60% of the world’s children have received a vaccine made in India and those vaccines that you know are available from Ser Institute or Barat or biological e or panasia have really saved millions of children the expanded program of immunization vaccine the usual childhood vaccines have saved 2.5 million lives a year since the decade of vaccines began in 2010 now if we were to fully Implement vaccination all over the world with those vaccines we’d save another 2.5 million that gives you an example of the scale and the impact of vaccination at the same time the infectious diseases for which no vaccines exist and now this includes hi V TB malaria and the rest killed between four and 5 million there are major problems because of global morbidity and mortality and we don’t have vaccines that can get companies interested in them because those companies are thinking well those who are going to get tuberculosis will not be people in the United States or in Europe but people in low and middle inome countries so they won’t be able to afford these vaccines that is exactly why philanthropic and nonprofit organizations are so important in the world of dealing with infectious disease who ends up paying for this governments high-risk research that’s done by um or philanthropic organizations like Gates or welcome trust the covid vaccines the MRNA vaccines would not have been possible had NIH not funded the more basic research to run mRNA and of course the sad story is that you know um Ki Caro couldn’t get funding from the ni which get again gets the idea that nothing’s perfect I mean this was a brilliant idea saved millions of lives but she got fired because she couldn’t get a grant to fund this work R&D is very important who funds high-risk R&D the R&D that makes a difference not not tomorrow but you know five years or 10 years or or 15 years later it’s governments and who and you know high-income country governments the governments of Japan of the European Union of the United States and Canada Australia fund that kind of research but for the things that kill people in the other parts of the world you don’t get the same attention you know we don’t get countries in subaran Africa or Latin America having large enough amounts of excess Capital so that they can make investments in in research in infectious diseases if you think about the funding that the NIH puts in it’s developed this huge R&D ecosystem in the US and in much of the developed world that R&D ecosystem underpins all the success that we’ve had in biomanufacturing technology it is critical so who does that for neglected diseases nobody if we talk about African vaccine manufacturing there’s no system of funding that develops the scientists who focus on the key research questions around that especially for diseases in in low to Middle inome countries no one can take it Forward into a manufacturing step and beyond that who is there to buy it exactly so it’s frustrating for me and I imagine you know Ministers of Health in the developing World um the global South so I asked Jerome how he felt in terms of the slow or failed approaches to neglected diseases since he comes across just so optimistic when we talk to him there are several approaches to to the mountain in front of you you can push your rock up the hill uh or you can be happy to advance one step at a time and um and I think in global Health we we see the hill and we can’t get our arms around it but as we make progress and it’s not only progress in health it’s progress in development that also informs um advances in health and being able to feed everybody being able to provide people with clean water being able to provide people with reasonable shelter being able to provide people with education we think of them as just development things and they are related to uh health and vaccination we know that if you vaccinate children families stay out of poverty we know that children’s level of educational attainment is higher we know that um development developmental and cognitive indices improve in vaccinated children so the great Improvement since the year 2000 with Gaby with the Global Alliance um for vaccines and immunization um is has been 2.5 million more children survive every year because of vaccination hopefully Co has taught us that Health Systems need to be strengthened vaccination systems could be better and it’s terrible that 20 million people died during covid in fact people are still dying of covid but vaccines prevented an additional 20 million deaths yes and we have to be satisfied that there were people people that we helped and if you lose your sense of optimism then you give up and there is no time to give up we’re making progress incrementally on a goal uh and I think many people feel that when I first went to Uganda driving along the highway from anbi to compal you pass these these strip malls at little places with tiny little stores and the biggest the biggest seller were the coffin because this was the time when everyone died of AIDS now when you go people are selling furniture and the stores and now when you go to many of these African cities you see these giant skyscrapers and you know there’s been there has been progress It’s been uneven you know in many of the African major cities with chlorinated water you can use water to to make formula because it’s safe you go outside the city and you’re better off having a bre the child breast fit uh so again there has been progress and um and Africa is making that progress and yes progress is uneven maybe what we can do is um is to allow other things to progress more rapidly including um strengthening of Health Systems and and vaccination one of the really amazing things that ivi is doing is working on Africa’s ability to run in region for region manufacturing absolutely making it happen where it is needed less than 1% of vaccines used in Africa are actually manufactured in Africa so so various groups have pledged $5 billion for vaccine Manufacturing in Africa all the things that go into that the R&D ecosystem for vaccines before you actually have manufacturing that is the Laboratories that help you to test the vaccine the clinics that help you to conduct vaccine clinical trials having appropriately mature regulatory systems that can actually say that vaccine’s been manufactured at high quality and it’s approved those regulatory systems don’t exist either if you’re trying to start a new industry how do you compete against a lowcost highquality producer like India and so who’s going to buy the vaccine and who’s going to use the vaccine because you know we had a situation where we were making anti-retroviral drugs in Africa they were more expensive no one wanted to buy them so we bought all the back all the drugs from African vaccine from Indian uh drug makers and the African industry died so again if you’re not thinking about vaccines as an ecosystem that starts with research and development goes through manufacturing and approvals and then goes to to purchase and uptake then you’re creating a system that doesn’t work and Ava we intend to create an African organization that can do what we do that can take a vaccine that a university has find funding from The Gates Foundation Move That vaccine through the laboratory in through clinical testing and through manufacturing and approval and uptake but you need an organization that thinks end to end and that doesn’t exist in Africa yet and so our big AA project is to try to create an organization that’s like IBI that could be a competitor to ivi that can do that but that is located and invested in Africa that is local and and strengthens systems locally so a big thank you to Dr Jerome Kim for sharing good yeah um real expertise on vaccine Supply and development for infectious disease but what about the diagnosis because it’s one thing you know being able to treat or be able to vaccinate against it but how do you diagnose it Dr Kim mentioned the Gates Foundation let’s let that lead on to our next guest my name is Karen Hegman and I’m a PhD scientist and I lead our Diagnostics program at the Bill and Melinda Gates Foundation and we work within the global Health Division and we primarily focus on diseases that affect the world’s poor and people that are underserved so those include TB HIV and malaria and in the case of covid of course all hands on deck we focused uh almost exclusively on covid during the pandemic times Diagnostics is a really broad topic how does Karen segment Diagnostic modalities and think about them in terms of making them accessible to underserved communities well one of the biggest gaps in care Cascade is the diagnostic Gap basically meaning that actually diagnosing is your biggest challenge in many cases depending on the disease there is some usually large fraction of people that actually go without a diagnosis and without a treatment at all so in the case of tuberculosis for instance it’s estimated that 40% of people that have a a tuberculosis infection actually never get diagnosed and never get treated in the case of malaria it may be fully 2/3 to 70% of people are never diagnosed and never treated which is really a criminal thought to to have in mind given that we have treatments that can treat these potentially lethal diseases and infections so um for us what we want to do is be able to identify those people that have a treatable disease and be able to get the medicines to them so our strategy is that while we have uh diagnostic tools that can be used for tuberculosis and malaria for instance they’re not reaching all the people that they’re meant to reach and there’s a number of reasons for that one reason is that often times people that seek care for these diseases they have symptoms and they want to be treated they don’t come to the right setting for where the testing is performed in the case of tuberculosis a person in Africa might have to travel many kilometers to a a complex laboratory or hospital setting and that’s really a barrier for for people to to get diagnosed and so the idea is in that case bringing access means bringing the Diagnostics to the [Music] people diagnosis of course is part one and then treatment is part two knowing what a patient has and then being able to treat that patient are two very different things because you might have a country system that can deliver diagnosis but not treatment or vice versa a national system that can deliver treatment but cannot deliver a diagnosis just being able to associate a person’s test results and their specimen with themsel as a unique identifier so that that person can be brought into the care system that’s actually a really big bottleneck because um we don’t have a way to get medicines back to people if the medicines don’t necessarily reside in the same places where the tests are done so having specimen collection devices that have barcodes on them that can be read by uh a mobile phone or a tablet makes it so that you can connect a person to their specimen and their specimen to a result and the result to potentially a pharmacy or a clinic or even a healthcare worker who could bring the medicines to a person ‘s home in South Africa they have really great networks that keep track of people that are on anti-retroviral therapy and if that person doesn’t come in for a viral load test they don’t come in to pick up their prescription then a healthare worker will be aware of that and will actually go to their home and make sure that that person receives medication and comes in for for testing and then subsequent treatment so it’s super important to work within the government infrastructure to try to bring tools to the people during Co I think we all learned that people can do actually a good job collecting their own specimen for certain specimen types we started with nasal fingio swabs which of course a healthcare worker had to collect but um we quickly learned that a nasal swab or saliva was something that people could collect in their own homes or their workplace and so we’re looking to adapt existing Diagnostics to use alternative specimens that people can self-collect and in some cases even do a self- test in that case again you need to make sure that if a person gets a positive test result they know what they need to do to get care as technology starts to enable more diagnoses does Karen have a view on whether countries should be focusing on screening for asymptomatic disease or focusing on diagnosing an already symptomatic disease countries typically are most interested in Diagnostics that impact care treatments for covid didn’t come until very late in the pandemic and in the case of getting a diagnosis there wasn’t necessarily a benefit to the individual to get a diagnostic test right but there was a benefit potentially to the community to the family to the workplace if the biggest interest and the focus of the country is on containment of the infection at a public health level then that may be a strategic question where they would want to apply Diagnostics to being able to affect behavioral change to keep people limited and isolated however the World Health Organization and most countries emphasize Diagnostics that have a treatment associated with them so I talked about tubercul is there are antibiotic regimes that are out there so people can get a test result and immediately initiate care with malaria it’s a bit of a different situation where um we’re not at a place where in most places we’re near elimination where we’re worried about spread so much but we are worried about people that present with fever that get very sick and so I think prioritizing diagnosis to initiate treatment ends up being more important in that situation than limiting spread what Karen said here is really interesting and interesting for me CU I have personal experience of malaria um myself and in my family um my mother are you listening mom um had malaria doing her iring she is doing her ironing had cerebral malaria and the diagnosis took uh rather a long time because nobody in the Netherlands which is where she was when she was finally diag diagnosed had actually seen a case like this in a long long time High inome Country High inome Country not expecting to be have to have malaria so super interesting and as the world warms up we are already starting to see cases of malaria in southern Europe and the southern part of the United States there are parallels between the way the wealthy North responds diagnostically and the global South so you and I being in the wealthy North right now how can our privilege help us stop the northward spread of malaria noting that poor Nations have been trying to do that already for 60 to 70 years I think if you look realistically and kind of cynically at what happened during covid the high income countries in the north basically um monopolized the supply chain and the capacity that was out there and that was particularly distressing for us I can tell you and we put a lot of effort and a lot of money in trying to develop Manufacturing Systems that could be much more highly scalable and low cost so that we could provide products to the global South and that’s something that we still have underway and is still a priority for us I think if we’re thinking about things like malaria spread into the global North what will probably end up happening is there will be screening efforts and tests that are required for travel and I could imagine that there may be interest in identifying whether people are bringing malaria into the country you can even test mosquito reservoirs and you can test other things more environmentally than um on the individual basis but realistically I think what may happen is that people in the global North would have mechanisms to test people that are bring that are coming into the country [Music] it’s pernicious isn’t it the progress that happens in the north is differentiated from what happens in the South when the problem becomes real for individuals in the north then we see action it becomes important yeah exactly what keeps Karen so positive in the face of such insurmountable odds I’m a natural Optimist and even though through covid I was in the trenches trying to develop and scale diagnostic uh tools and specimen collection devices I do have the hope that technology can help solve some of the biggest questions being able to find new tools that people can use to as I said collect their own specimen can we uh scale those appropriately make them readily available so preposition collection devices with barcodes so that they’re ready at the first sign of infection that people can take control Ro of Their Own healthare by initiating diagnosis is one of the strategies that I think is gives me hope that we can give more control into the hands of the people the one thing too that we’re thinking a lot about is manufacturing in the regions where the diagnostic products are meant to be used and then you have more Countrywide and Regional autonomy to having products and Manufacturing readily available and so even develop developments that happen in the north can be technology transferred to countries and regions in the South and um hopefully they’ll have their own ability to manufacture the products that they need the most and prioritize the tests that will make the biggest impact in their [Music] regions and this really is hopeful right Karen joined the Gates Foundation just before the pandemic so she literally had to Dive Right In I have been working in diagnostics for the last 15 years or so and I had an opportunity from a former colleague to that was working at The Gates Foundation to take over his portfolio upon his retirement and I really wasn’t looking for a change I had built a great team and I had a great job but the potential for impact was so taning that I just didn’t didn’t feel like at this stage of my career I could pass up an opportunity and little did I know that a global pandemic where Diagnostics and specimen collection were going to arise and I would be faced with a critical challenge but it I I would have to say it’s the most rewarding thing that I’ve done in my career the whole work that we did around nasal swabs as an alternative specimen type we drove that entire work stream through um the usfda adopting it as a specimen type getting the public good of all the information the labs in the US adopted it I shared information about the methods on a daily basis many times a day with the CDC with the UK government Canadian government all my grantees in Africa wh and um to see something that you were a part of and have it really be applied to a health condition and emergency setting is kind of theam I would never wish for it again but it really brought through my hopes for making a big career move like that today we’ve talked about the steps needed to improve access to healthc care in underdeveloped and lower middle- inome countries we’ve talked about two sides of the coin with vaccine development and supply and then improving diagnosis and I’m walking away from this conversation feeling that whilst it’s still got a long way to go to where it would be if it was Equitable that important steps are being taken what are you walking away with doie well both of the scientists we spoke to today are optimistic so the closer you are to this topic apparently the better you feel about it so I’m feeling helpful maybe we should get closer to the topic and dive in a little bit further and I mean our own biofarma resilience index shows these gaps between the global North and the global South so it is a topic that will take a long time to solve if ever it is solved but it’s certainly a topic that is Rich for discussion it is it is so now why don’t we turn to our every day is a school day section yes our regular section shall I go first or you what have you learned this week well I saw a nice article in neuroscienc news.com that is uh appropriate for the everyday is a school day section and it’s about dopamine and it’s about the role that dopamine plays in encoding both reward and Punishment errors in the human brain and there was me just thinking dopamine was just reward exactly it’s just that social media feeling of when everybody um when people like your post and you feel that Rush that’s dopamine but this study actually looks at how does dopamine encode both reward and Punishment in the human brain very very fast it happens very fast so I thought that was kind of cool that is very cool talking about reward receptors in the brain um I’ve been listening to a really good podcast for quite a while now it’s called Discovery matters it is indeed and the other one that I also listen to from which we take some inspiration I’ve got to say um is one with Wendy Zuckerman called um science versus and Wendy has just done an episode on caffeine oh cool and the effects of caffeine and whether it’s good or not and so on and so forth and one thing that I didn’t know was that caffeine doesn’t do something to give you an extra bit of Zing it just stops you from being sleepy so caffeine binds to receptors in the brain which would otherwise be bound to by ad noine which is the neurotransmitter which makes you feel sleepy so by blocking that neurotransmitter from being bound to in the brain it stops you from being sleepy so there is in fact a point at which no more caffeine is going to keep you more awake which is when all of your adenosine receptors are taken up with caffeine and then coffee is just going to make you want to well depending on your genetics maybe go to the L A bit more maybe I’ll but you know what I’ll drink to that scking with my shots every day [Music] totally our producer is Beth armit Brewster editing mixing and supervision by Banda Productions Music from epidemic sound my name is Dodie axelon I’m grateful that you’ve been listening and I am Connor mcne also grateful make sure you rate US on Spotify or whichever platform you use it helps us somehow we’ll be back soon with another episode of Discovery matters [Music] [Music]
Challenges of improving access to healthcare in developing countries – it’s a conversation we need to have. With the help of Dr Jerome Kim, Director General of the International Vaccine Institute, we discuss vaccination and immunization programs as a key aspect of public health and global development – especially in developing nations, where access to life-saving medicines is often limited or non-existent. Karen Heichman, Deputy Director of Diagnostics, Bill and Melinda Gates Foundation, takes us on a journey of the critical role of diagnostics in the fight against diseases.
Tune in to hear how technology and innovation could help to bridge the gap in access to healthcare and potentially save lives in the process.