New tools to fight tuberculosis | 91TV
Transcript
- Richard
- Catlow:
- Well, good evening and welcome to this Africa Prize lecture. Welcome to the Royal Society. My
- name is Richard Catlow. I'm a former foreign secretary of the Society. I've also for many
- years had the privilege to have scientific collaborations with South Africa and other
- African countries, and so it's a great pleasure for me to be here this evening.
- Before we continue, just a few housekeeping notices, please do make sure your phones are
- off! I turned mine off just before we came down. There are no planned fire alarms,
- so if you hear the fire alarm, we need to go and you need to go by the exit, there's one there
- and you assemble outside, at the top of the Duke of York steps to the right of the Royal
- Society, but hopefully that won't happen. Well, this evening's lecturer is Professor
- Novel Chegou, and let me say a few words about him before I tell you about the Royal Society Africa
- Prize Novel is currently a full professor of Immunology and works in the Division of Molecular
- Biology at Stellenbosch University in South Africa, where he received his PhD back in 2009.
- He heads the TB Diagnostic Biomarker Research Laboratory, which is an independent research
- laboratory. It's part of the larger Stellenbosch University Immunology Research Group.
- Novel has received a number of awards, including a silver medal from the South African Medical
- Research Council, a Rector's Award for a general performance from Stellenbosch University and an
- Emerging Research Talent Young Researcher Award from the UNESCO-Merck Africa Research Summit. So
- already has shown his distinction as a scientist. Now a few words about the Africa Prize. It's
- awarded annually to recognise research scientists based in Africa who are making
- outstanding and innovative contributions to the biological and physical sciences,
- which contribute also significantly to capacity building in Africa. The prize is intended for
- researchers at a fairly senior stage of their research career, and with the potential to
- build a research project to follow on from the prize and we'll award the certificate and medal
- at the end of the lecture. It's now my great pleasure to welcome Professor Novel Chegou to
- present his Africa Prize lecture on Tuberculosis control: the need for new tools, Professor Chegou.
- Novel Njweipi Chegou:
- Thank you very much, Sir Catlow, and thank you to everyone else for making time to join us. I can
- see quite a few faces that I know. I also want to recognise the presence of the South African
- High Commissioner. It's a very huge honour to have you here. Thank you for joining us. I'm
- going to talk a little bit about tuberculosis. Just give you some statistics, facts about TB,
- that would go to the challenges that we have in controlling TB. Then I'll of course tell
- you a little bit about where I come from, what we do and then have some concluding remarks.
- Well, tuberculosis in short TB is a disease that is caused by a bacterium
- called Mycobacterium tuberculosis is a disease that mostly affects the lungs, but it can also
- spread to other organs of the body as you will be, as I'm going to be talking to you about.
- TB is a disease that kills one person every 20 seconds. According to the statistics that
- were published by the World Health Organization recently, in 2022 report, it was revealed that
- TB killed nearly 5000 people a day in 2021 and in that same year about 10.6 million people were
- estimated to fall ill with TB. Now how is this disease transmitted? So when somebody has TB it's
- transmitting, it's spread from person-to-person through coughing, sneezing, talking or singing.
- So when somebody who has TB coughs it produces these aerosols. I think I need to get online, just
- one moment. Yes it produces aerosols which contain the bacteria that that that cause TB. If you as an
- infected person, an infected person is close-by, you breathe in these aerosols and they get into
- your lungs and that's how you get the infection. So I must clarify that it's not everybody that
- gets infected with TB that has the disease. In short, if you look at in fact, if you look at
- some of the communities that we work in in South Africa, you will notice that up to 80 per cent
- of people in those communities are infected with… Harboured the bacterium that causes TB, but only
- 92 per cent… And 90 per cent to 95 per cent of these people will never become ill, meaning that
- the 10.6 million people that develop TB every year are just part of this. Five per cent to
- ten per cent of people that are infected with the bacterium that causes the disease.
- So in short, if you have latent TB, when you have latent TB, you are not ill. You cannot
- transmit the bacterium to another person, but under certain conditions for example,
- when you become immunosuppressed as a result of HIV, immunosuppressive drugs,
- then now you have active disease and then you start having symptoms and then you are able to
- spread the disease to other people and you may die if you're not treated. So like any other disease,
- proper control of TB depends on vaccination, early and rapid diagnosis of the disease and also
- ensuring that people who are diagnosed with the disease are put on treatment as soon as possible.
- When it comes to vaccination, we have a vaccine that I will call in short BCG, which has been in
- use for more than 100 years now in high burden countries such as South Africa. The vaccines are
- administered to children before they leave the hospital shortly after birth, before they leave
- this hospital to go home. Like I said, it's been used for a long time. It has a very good safety
- record. The problem that we have the vaccine is that it doesn't protect you. It doesn't give you
- long-lasting immunity. So in fact, by the time you get to your teenage years, you've lost most
- of the protection that you had from the vaccine. So there are a lot of studies that are ongoing.
- New vaccine candidates that are coming into the picture which are being tested, and we are hoping
- that very soon we will have some candidates that will maybe help us replace BCG, or help enhance
- the immunogenicity of BCG, or maintain the immune response that is generated through BCG.
- When it comes to diagnosis, the gold standard way of diagnosing TB is by growing the bacteria
- in the lab. So TB culture, unfortunately TB is a very slow growing organism and it may take
- up to 42 days before we get results. Imagine it's a disease that is spread by aerosols,
- and there's somebody out there waiting for test results to come out for 42 days. Imagine how
- many people would have infected at that time. So the other issue that we have with this test is
- that it's very expensive. It requires a special facility which is biological safety level three
- environment. I can tell you now that in some African countries we only have one lab that is
- able to offer that test which is not good enough. Then so because of the difficulties in, yes,
- because of these challenges in administering this gold standard test, you see that a lot of labs
- that test for TB, according to this survey that was published in 2017, a lot of the labs still use
- the microscope to diagnose TB. The problem that we have with microscopy is that although it is rapid
- test. Don't get me wrong, it's very rapid and it's cheap. The problem that we have with it is that if
- you test 100 people who have TB, you're only going to get results, positive results in 60 of them. If
- it's a population that has high HIV infection, then you're looking at 20 to 40 people that will
- come out with positive results. So it's not really good enough.
- Recently we had molecular assays that came into the picture. The key one that we've been using
- is the GeneXpert, it's relatively rapid, it can give you results within two hours.
- It's highly recommended by the World Health Organization. The issue that we have with the
- GeneXpert too is that it requires electricity. Being like somebody who comes from Africa,
- I know there are African countries that you can stay for up to four days without electricity.
- Imagine that you're going to administer this test, power goes off, then you can't get any results.
- So a test that is supposed to give you results within two hours suddenly becomes a very long
- time before you get results, if you manage to get back, go back to the hospital to get the results.
- So according to also this survey that I also referred to here, this survey found out that up
- to 25 per cent of laboratories that are supposed to be testing for TB are still using methods that
- the World Health Organization banned more than ten years ago. Why are they resorting to these
- methods? Because they are easy to perform its rapid test, even though they are not very useful.
- So when we talk about the challenges that we have in diagnosing TB, most often we are talking about
- pulmonary TB. That is TB that occurs in the lungs. If you look at this publication that came up all
- the way reviewed article that was published in 2004, you see that even way back then,
- we already knew that in immunocompetent people, that is people who don't have anything wrong
- with their with the immune systems. Up to 15 per cent to 20 per cent of TB that they suffer occurs
- outside the body. That is TB that occurs in other regions such as the lymph nodes, the bone and
- joints, the meninges, etc. and when it comes to HIV infected people, that proportion increases.
- Now if we say diagnosing pulmonary TB is difficult, it's actually a lot more challenging
- to diagnose, this one, this type of TB. I'll talk a little bit about that later. So one of
- the main limitations that we therefore have with this existing test is the reliance on sputum. So
- sputum is imagine asking a child to cough and give you a material that you can use in in the
- test that we mostly use now to diagnose TB. It's almost impossible. A child will cough, swallow it
- and then just give you back saliva. So we urgently need tests that are based on material that we can
- collect from all patient types, regardless of whether they are adults or children. Some
- of the sample types that we are looking at are blood, saliva, urine and other fluids.
- So in this day and age, if we want to develop a test that will be useful for diagnosing TB, I also
- think it would be great if we ensure that it's a test that people can use at lower levels of the
- healthcare system. I'm talking about your nurse who works in a health post somewhere in remote
- environment. The WHO already recognised this need and published a report about the characteristics
- that new test should fulfil if they are to make an impact in TB. This was published all the way back,
- way back in 2014. If you look at the top two types of tests that they recommend,
- it's a point of care non-sputum based test, a test that is able to detect all forms of TB. The second
- one is a point of care, what they call it triage test, which is supposed to be a simple low cost
- test that can be used by first contact healthcare providers again like your community healthcare
- workers to rapidly diagnose TB and hopefully put people on treatment as soon as possible.
- Now you would think that diagnosing TB is our only problem, but far from it. TB treatment
- is a long process that lasts for a minimum of six months. If you have TB that is outside the lungs,
- it may even last up to 12, you may be on treatment for 12 months and if you have
- multi-drug resistant TB it may take up to 24 months. A lot of these patients die just within
- a few months of beginning treatment. Besides the long duration of treatment, there are patients
- that start TB treatment. After they get to month six when we were expecting that they are cured,
- you do a TB test, it comes back positive. So we call that treatment failure. So treatment did
- not work for reasons that we don't understand. There are other there are other patients that
- you test. They return a negative result. Then we are shouting hey, this person is cured. Within two
- years of completing treatment, these patients come back with TB and sometimes when you test them, try
- to look at the genomics of the bacterium that you isolated from their sputum samples. It's exactly
- the same strain that they had long ago when they initially had TB, which is what we call relapse.
- So the challenge that we have in this area is about developing tests that we can give to
- clinicians, for example, in saying, okay, before you start treating this patient, maybe do this
- test and if it is positive, then there is a high chance that maybe this patient will not be cured
- successfully, or it will mean that this patient have poor outcomes. So we've been looking at what
- we call biomarkers that may enable the development of this test. Or we can say treat the patient for
- two weeks. Look at the concentrations of these proteins in the blood. If it doesn't change
- by a certain level then maybe do something more, maybe change the course of treatment
- or try to moderate the treatment somehow. Now that I've told you a little bit about
- the issues that we have about TB, I think let me tell you a little bit something that
- is a little positive about where I come from. So I was introduced, I was introduced I work
- at Stellenbosch University Faculty of Medicine and Health Sciences. If you were to Google that
- you are going to find a picture like this one. The white buildings that you see are
- the medical school and the brown buildings at the back are the Tygerberg Academic Hospital.
- It is the second largest hospital in South Africa in terms of bed capacity. Yes,
- and it's the training hospital for our university. Now if you visited me about three years ago,
- you would have met me in this building and probably parked your car in this spot.
- Now, if you come to visit me today, you'll be amazed at this brand new modern, state of the art
- 1.2 billion rand building that was constructed for us by Stellenbosch University with support
- from the South African government. It is all South African money, no foreign funds coming
- from anywhere. In this building we have really nice state of the art facilities, some of which
- are like the first in the Southern hemisphere, including this biorepository which is an automated
- storage system. If you want a sample, all you need to do is talk to the computer. It goes,
- picks it up and brings it for you. We can store 3.5 million samples, up to, with the capacity to
- expand to even 5 million. There are a lot of other things, not just the facilities, the equipment
- that we have in this building. We have also nice people, nice researchers that are onboard to help.
- Then if you go within this environment, I work in a team that is called Stellenbosch
- University Immunology Research Group also as was introduced. So, we are a group of scientists that
- share an accredited laboratory, and we are led by a distinguished Professor Gerhard Walzl, and
- Gerhard is also the head of the Department of Biomedical Sciences, which is the main department
- that is in the new building that I just showed you. Under him are other people like myself. I
- work on biomarkers and diagnostics as introduced. A colleague of mine, Andre Loxton, who works on
- research, focuses more on B cells. Professor du Plessis work focuses more on cellular immunology,
- and we have Dr Juliana Klein, who works on immune endocrine interactions in the context
- of TB. All of us work together with Professor Stephanus Malherbe, who heads our clinical team.
- That team alone is about 50 on average, about 50 people or more and includes specialist doctors,
- nurses, drivers all the kind of people that you need for the kind of research that we
- do. Additionally, we have our own bronchoscopy suite, which means we can perform really complex
- studies on patients without interfering with the service that is offered at hospitals. We have a
- team that designs and manages our databases. These two ladies actually there are three of
- them. I forgot to put the picture of one of the other ones, Ilana, here. They are,
- the engine powerhouse between our lab, because they do the lab management and
- quality control and we have a bioinformatics team that is led by Professor Gerard Tromp.
- Besides collaborating with these colleagues, I work a lot too with other colleagues who are in
- the rest of the faculty. One of the main people that I work with is Professor Regan Solomons,
- who is a paediatric neurologist and the head of our Division of Department of Paediatrics
- and Child Health. I also work with distinguished Professor Perold, he's an engineer. So what we're
- trying to do with him is to start introducing engineering students to biomedical research,
- just to spur some of them to start maybe thinking about product development and so forth. So
- although we have a good bioinformatics team, I still work a lot with Professor Martin Kidd,
- who heads the Centre for Statistical Consultation of Stellenbosch University. Out of all the
- students that I have and I think I currently have 12 students, I chose to put the picture of one of
- them, show the picture of one of them on this slide and this is Candice Snyders who she was a
- technical officer, senior specialist on one of the platforms that we use, and she's now doing a PhD
- under my supervision. Yes, a lot of people tell me that, oh, we want to come to Stellenbosch and do
- especially Luminex with you, but when you come to the lab, this is the person that hand you to. Yes,
- you're going to continue working with her. So yes, she's been a great help in the lab.
- Now as introduced I work on biomarkers for TB. So what about markers?
- So biomarkers are basically anything that you can measure objectively which can tell you that
- a disease is present or some pathological process has occurred. In the context of TB
- we know that when a person is infected with TB the immune system doesn't just sit there. The
- immune system fights, tries to eliminate the bacterium. As your immune system is fighting,
- it produces these chemicals that are released into your circulation or into other biological
- fluids. This could be proteins, changes in gene expression. It could be metabolites. So what we
- then go and do is to come out of all the thousands of molecules that the immune system produces,
- which of them are specific for TB. We try to use those as a method of diagnosing the disease.
- If you look at the work that we published about ten years ago, you observe that the focus was very
- much on screening of new TB antigens and also looking at biomarkers that are produced after
- blood cells were stimulated with these antigens. What we hope to achieve then was to develop point
- of care test that can make use of combination between new antigens and new host biomarkers,
- which we could roll out. We did this through several large studies, including the G6 study
- where I got to work with so many people, including Professor [unclear name 0:24:55.5] who is here in
- the audience. She actually pioneered this whole blood assay that we were using in that study,
- and we subsequently moved to other studies, other studies like the AATBC and yes,
- we were a bit a little bit successful, successful in this kind of work.
- We want to develop tools that are rapid and tests that are more easily applicable,
- especially in resource poor settings. A lot of what we have been working on recently has been
- on biomarkers are detectable in those samples that are easy to collect from all patient types.
- I'm talking about your blood, saliva, urine or other biological fluids. These are just
- some of the platforms that we use to when we are evaluating looking for these biomarkers.
- So where have we gone to? How far have we gone with this work? Well, one of the most prominent
- papers that we published on this work is this one that I'm showing to you, where we discovered,
- we identified seven proteins that are detectable in blood and which showed a strong potential as
- diagnostic candidates for TB. Over the years we've been trying to validate these proteins.
- A PhD student of mine who is now graduated took these findings further and validated them in
- a large cohort of African, of samples that were collected across all of Africa. We try to reduce
- the proteins to two or three biomarkers instead of the seven. Other colleagues in collaboration
- with other colleagues especially like this paper that I've shown here is work that was led
- by Dr [unclear name 0:26:28.7], who's here in the audience and other colleagues at Imperial where we
- try to look at do these proteins work in different secondary levels of the healthcare system in
- patients that majority of whom are HIV infected? Through work that was done by another PhD student
- of mine who just graduated, Dr [unclear name 0:26:47.9], who graduated earlier this year.
- We also tried to look at the utility of these proteins in samples that are collected in low
- burden settings. In this case, these samples came from Norway and Sweden. So throughout all these
- studies, we have seen that the key protein biomarkers that are useful in diagnosing TB,
- we are picking them up. We need to tweak the signatures a little
- bit to make them applicable to all sites. Where have we ended with this work? Well,
- also through collaboration with other investigators through other large,
- funded study, our colleagues at Leiden University in a team that is led by Professor Paul Corstjens,
- have developed this finger prick based test. The way the test works is you prick the finger
- of a patient, somebody that is suspected of having TB. You collect a little bit of blood,
- you mix with a liquid that you put into a test card, and after it dries, then you read the
- results and it can tell you whether the person has TB or not. So disclaimer, the test does not
- really look like this, this is just a picture that I've put. The actual test does not look like this.
- So where are we with this work? This test is now undergoing field trials in a number
- of studies that are that we are conducting in African countries and in Asia, but with
- support from organisations such as the NIH and the EDCTP. So we're looking forward to seeing
- how this test performs in real world settings in these studies that we are that are ongoing.
- Now, you notice that all I've been talking about is protein signatures. There's a lot of work that
- we're also doing on looking at gene expression biomarkers. Some of this work is not led by me,
- for example, per se, but in collaboration with other investigators, including the team at
- Imperial College, some of whom are here. So in this particular study, we got some
- funding from the South African Medical Research Council through which we try to look at all the
- gene signatures that have been published. We look at the top 96 genes that were in those studies,
- and we try to see if we could use them as a means of diagnosing TB in patients that
- self-presented at entry level to the healthcare system across a few African countries. What we
- are observing is that some of these signatures continue to perform very well. Yes, they perform
- relatively well in these patients, although none of them is perfect as yet. Yes, this is a study
- that we still we're still analysing the data and we'll be seeing more of this in the near future.
- This other work that we're doing in children, in patients that have extrapulmonary TB. I
- thought I include a few slides about a form of extrapulmonary TB that I got introduced to
- not so long ago, compared to all the other work that I've been doing. I'm talking about
- tuberculous meningitis. So TB meningitis is the most severe form of TB. It affects
- mostly children and HIV infected adults, and it leads to a high number of deaths in children.
- Actually it is estimated that even if you diagnose it on time, 50 per cent of people
- that suffer from the disease will either die or suffer from neurological problems if treated.
- In children particularly, it's about 20 per cent that will die if you diagnose them when they are
- diagnosed with this disease. Most of the issues that we have with this disease are not because of
- a lack of treatment, but they are just a result of delayed diagnosis. Then again, if you look at the
- study that was published by my collaborators from Tygerberg Hospital, they observed that it took
- patients, it took caregivers six visits to a hospital before the disease was diagnosed in
- children and by then it was often too late, which is what contributes to the poor outcomes that we
- see. So if your child comes early to the hospital, you can see it's relatively still okay. Sometimes
- the child comes in this form like stage three TBM and the outcomes are not great at that time.
- I just included these two publications out of the many that you can read about this disease
- if you want to. If you're interested in learning more, these are two papers out of the many that
- are out there that you can read up. So but after being introduced to this disease, we started
- asking ourselves is there something that we could do? Could we use the same methods that we're using
- to conduct research in adults on these children? So what we have been doing is collecting samples
- from children that are admitted to Tygerberg Hospital and then collecting basically the same
- samples that we have been collecting in adults and trying to see if we can identify biomarkers that
- we can use to easily diagnose this disease. In the first study that we did, which was a
- collaboration between us at Stellenbosch and people at VU Medical Centre in Amsterdam,
- we identified three proteins which when you measure in the body,
- had potential in diagnosing this disease. After we saw these findings, I went and applied for some
- funds from the South African Technology Innovation Agency and we had a little bit more money and
- we refined. We were able to refine, refine our signature, improve it with new proteins and
- improve the diagnostic accuracy a bit. At the same time, in that study, we tried to look at,
- we started looking at blood based biomarkers and we came up with some candidate biomarkers that are
- detectable in blood, which showed a potential too. So over the last few years we've been trying
- to verify these findings to really check do these things really work as we think they are
- working? You don't need to read this table. If you look at what I've put here in red,
- we're showing that none of the tests that are currently existing for diagnosing that disease,
- actually work as good as some of these biomarkers that we have been working with. So there is hope
- that we may be able to diagnose this disease sufficiently using biomarkers.
- Because the technology that we use is a research based tool, it's not a test that can you can use
- in hospital. We started trying to translate that into tools that can be used at the hospital.
- One of those techniques is called ELISA. ELISA is something that you cannot really do it at the
- lower levels of the healthcare system. You need good hospital, trained personnel to do that. We
- try to see whether if we converted these things to ELISA based format, do they still work? Yes,
- if you look at these figures, a perfect test by the way, for a perfect test,
- this curve should be all the way here, should cover the whole of this space. So you can see
- the biomarkers, they continue to show potential when converted to ELISA format. When we look
- at the proteins together we are able to get the same accuracy that we got with the more
- expensive research based tool that we are using. What about biomarkers that are detectable in
- blood? Well, we tried to validate the blood based biomarker that we, signature that we identified
- earlier. For some reason we could not measure some of the one of the proteins in the blood from
- the children we are working with. If you look at the other two then it's still we're not too sure,
- we need to do more studies, at least get the other protein involved. When you look at that
- signature in adults and these are adults who had meningitis, 75 per cent of them were HIV
- infected. You see that that that tells that we developed for children is pretty useless. It
- doesn't work in adults. So after through careful looking at the data, we are able to come up with
- up to nine proteins in children and up to five in adults that seem to show potential. But we
- still need to do more work in this area. So what next for the TBM diagnosis. Well,
- I showed you some data that shows that work that we've done, revealing that
- biomarkers that are detectable in cerebrospinal fluid may have potential in diagnosing TBM. The
- next step is to try and incorporate these biomarkers into a simpler test format. For
- example, your glucometer, the test that we use for measuring blood glucose levels, something that's
- similar to a pregnancy test, for example. So that is work that is still ongoing. We know that
- the challenge that we have with that test is that it's not easy to collect cerebrospinal fluid from
- children. So what would make more sense is a test that is based on blood, because that one can
- easily convert into a point of care test, and so we are going to continue. We continue to work on
- refining the blood based biomarkers to see if we can develop a test that is based on blood.
- So yes, I'm getting to the end. If you look at where I started in the beginning, I mentioned
- that way the TB field is eagerly awaiting the development of new vaccines and new drugs,
- to use to treat the disease. While we wait for these tools, vaccines and new drugs to come to
- the market, it is very important that we are able to diagnose patients who have the disease
- as soon as possible and place them on treatment as soon as possible. In when talking about tests
- for diagnosing, especially adult pulmonary TB, I mentioned that there are a couple of projects that
- are ongoing globally. Many people have identified biomarkers that are showing potential. There are
- many point of care tests that are under development for diagnosing the disease. We
- need to do more in trying to see whether we can actually diagnose, identify these proteins in
- easily collectable samples like urine and saliva. The problem with of diagnosing TB in children will
- remain. But I'm glad that especially like the team at Imperial, the colleagues led by
- Professor Michael Levin who is here, have been privileged to work with them on some projects
- where we're trying to look at both proteins and gene expression signatures to diagnose TB,
- and that work is very promising. So we're hoping that some of those get converted to
- point of care tests in future to help diagnose this disease. As we work on those proteins,
- it will be good that we also see whether they are useful in monitoring response to TB treatment.
- Yes, my last slide. So one other thing that we also need to continue doing is that we as we
- validate these proteins, we need to start thinking about the settings where this test will work. If
- you say you've developed a biomarker based test for TB, this is a rapid test that we've developed
- for diagnosing TB. Then we don't know whether it works well in people who are HIV infected.
- We don't know whether it works well in patients who have diabetes. So we need to validate these
- biomarkers in all kinds of patients so that we are able to say to an end user, okay, for this
- particular test, don't use it in this kind of patient, or use it only in this kind of patient.
- Before I go, I would like to tell you a story about this picture that I put here.
- Well, in March 2020, I and one of my colleagues, Candice, whose picture I
- showed you, were in Germany trying to work on a project with some colleagues.
- Suddenly we heard that Germany was going to close all its borders. So we had to rush to get out of
- the country to get back to South Africa because we do not want to be locked in, in that country.
- Just a little over two years after that, my very first meeting after borders were opened was in the
- UK. So I came to the UK, got to the room that was kept for me and I saw all the other normal things
- that they put like towels and other like. When I looked on the table there was this small box. I'm
- like oh but what is this? So as I opened it, what I saw was this thing a COVID-19 self-testing kit.
- That got me wondering. It was just two years I was running away from Europe because of COVID,
- and I come back two years, after we had vaccines, we had diagnostics, including tests that people
- can self-test, that you can test yourself. Then I started thinking about TB.
- This is a disease that has been killing people for more than 9000 years. Like I told you about TB
- meningitis, women or caregivers have to take their children to the hospital up to six times before
- the disease is diagnosed because we do not have this kind of technology. So then you can imagine,
- do TB patients not matter, do their lives not matter? So I think we can do a little bit more in
- our push to funding TB research in developing new tools for TB. As we start developing those tools,
- it would be great that we collaborate more with biological scientists like us,
- collaborate with point of care test developers, engineers and as we do that. We also collaborate
- with policymakers so that we are able to bring any test that we develop new tools to the market
- because it's not used. If you develop a test, you know that it works as a scientist, but the person
- that is supposed to take it to the patient does not know about it. So we need to talk to these all
- these people as we work on these kind of things. So to conclude, I would just like to acknowledge
- a lot of people. There are so many names, so many people that have been
- collaborating with over the years thinking about my collaborators within Stellenbosch University,
- people in the rest of South Africa, the rest of Africa, and the rest of the world, including here
- in the UK and other European countries. A lot of names that if I start mentioning people's names,
- I will take a while and I will forget some people. I also want to thank the members of
- the Stellenbosch University Immunology Research group is a big but fantastic team. Without them,
- this kind of work that we do will not be possible. There are two names that I want to mention,
- single out, is Professor Gerhard Walzl. He's my boss, is somebody that I'm working with since
- 2005. The good thing about him is that he gave me the opportunity to do my own thing, really.
- We worked together, but he gives me the freedom to think, do my own thing and then still go back
- to him and like, so mentored me, which was great. Then somebody like Paul van Helden, many people
- would not imagine, or would not expect me to put his name here. I will never forget the day that
- Paul… I went to, it was in 2004, I went to Paul's office together with my brother and we got there
- and we just said, told his secretary, 'We are here to see Professor van Helden.' She's like, 'But
- you guys don't have an appointment.' We're like, 'Yes, I know that we don't have an appointment,
- an appointment, but can we see him?' She went spoke to Paul. Paul came out of his office and
- took me in. We started chatting and within a few minutes he already gave me the opportunity. He
- said, 'Now when do you want to come and start?' So he was willing to give me the opportunity
- immediately. It was after that. Then he took me to the late Professor [?Tommy Victor 0:41:28.4]. We
- chatted more, then they realised that no, what I wanted to do I would be better supervised by
- Gerhard. So then they took me to Gerhard. So I still I appreciate him for recognising me
- immediately he saw me without asking questions. Of course I would like to thank all the people
- that have been funding this research, my family that has been supporting. Lastly,
- but not the least, the Royal Society for giving me this platform to talk to you. Yes,
- I also thank the man above for all the strength and thank you for listening.
- Richard Catlow: Well, thank you for that very exciting lecture that's really shown
- us how your work is responding to a major public health challenge. I thought your
- comparison at the end with the development of the COVID test was very, very to the point.
- We have plenty of time for questions so, and we've got questions online as well. So who would
- like to go. Yes. Wait until the microphone comes to you before putting your question.
- M1: Hello? Yes I have two questions. First one is perhaps quite naive, but why can you
- not take the technology in the West that's been used for treating TB over whatever period of
- time it is now? I don't know, but a long, long time to directly apply that in Africa. That's
- my first question. The second question is how rapidly does TB mutate and is that a challenge?
- Novel Njweipi Chegou: Okay. So when you talk about technology that's used for treating TB,
- it's the same technology that we use by the way. It's the same technology.
- So there's no difference. It's just that there are more resources here. For example
- I was talking about power failures, the lack of constant electricity. Since I came here,
- I've been expecting power failure, but nothing has gone!
- Richard Catlow: Not having load shedding yet!
- Novel Njweipi Chegou: There's no load shedding. So, yes, but that's a challenge that we have
- down there which makes the things that make the difference. But it's the same technology. Then
- the second question I think you asked about how soon TB mutates. It's not really a lot about the
- mutations. It's not really about mutations. It's about getting access to the patients.
- It's about getting access to the patients. There are a lot of people that get diagnosed with TB,
- and by the time they we know that they had TB, these patients have long gone. They are not in
- the hospital anymore. To find these patients, remember these are poor people. Some of them
- struggled, it's a disease of the poor. If you look at in South Africa, for example,
- some of the houses that is posted in its tiny place, lots of all the family members in one room
- and you have to struggle to feed their family. Then after somebody comes and does a test and you
- call this person after a few weeks and say, 'Oh, by the way, that TB test that you did is positive,
- can you come to the hospital?' Then this person starts thinking, do I have to take the little
- money that I have and pay transport to go to the hospital or buy bread for my
- family? So those are the some of the things that play against, not really so much about this, but
- some of the challenges that we have, and why TB continues to be a problem.
- Richard Catlow: Thank you. I think there's a question here.
- M2: Can I see a few words?
- Richard Catlow: Yes. Yes, of course. We're just waiting for the microphone to come.
- M2: I'm Doctor Hamid and I have a company in Africa, South Africa. You mentioned latent TB,
- you mentioned TB. You did not mention resistant TB. I'm more on the side of the medications, today
- according to what I read, the TB programme with rifampicin, isoniazid, pyrazinamide and maybe a
- quinolone is nine months. We have now also got rifapentine, the new drug, which could cut down
- the period from nine months of treatment, to four months of treatment. You then have bedaquiline for
- resistant TB. So there are medications that are there today for TB by and large, and I don't know
- whether Africa should start manufacturing their own drugs for TB. That's number one.
- We also manufacture and give you a drug called Q-TIB. It contains four ingredients and this is
- for children, paediatrics that are HIV positive and could get TB. So it's a regular treatment
- that could be given along with HIV drugs to stop children getting TB. So there are
- medications there. I think Africa should now try and develop their own newer medications. There
- are medications also that enhance the treatment using rifamycin, rifapentine, rifabutin. In India
- they have just developed a drug which you can use as an aerosol inhaled drug with rifabutin.
- So there are many new drugs coming up for TB that I think you could share with India, because
- India is a TB capital of the world and we can share with you whatever you require. Thank you.
- Richard Catlow: Thank you. Would you like to comment?
- Novel Njweipi Chegou: Yes, thank you for that, those comments. Yes. So you will notice that my
- talk was more focused on the biomarker side, the diagnostic side and the lab side because
- I'm a lab scientist. I think all the medicines, all the medications that you're talking about,
- we tried a lot of those clinical trials also took place in South Africa. The lab that I was doing a
- lot of those trials was actually in our building. But now TASK has moved to, they have their own
- facility now. So we have some of those in South Africa. The question is are they being rolled
- out to every TB patient? Yes I'm not part of the TB programme so I will not have all the answers.
- Yes, maybe I know that we're using some of those drugs at the moment, we're using them.
- Richard Catlow: Thank you. Question there, I think there are two there's
- one there and then one further forward. We'll take the one at the back first.
- M3: Yes, okay. That's very informative talk. I'm from Malaysia, I'm a paediatrician from
- Malaysia. I would like to just ask further on for cases like that. We have cases like
- with diagnostic patients with present with typical clinical history and findings of fit
- into a diagnosis of tuberculosis. They are smear negative TB and could not get any laboratory
- diagnosis could not get any histological diagnosis to support TB. These kind of patients improve
- empirically with the medication of anti-TB. In the lab perspective in your expert area, I was
- wondering whether these cases which we cannot identify any laboratory or biochemical support
- of TB, and yet they have a typical presentation of TB and the management may fit into the diagnosis
- of TB. How far can we get some support from the lab in terms of the specificity, the sensitivity
- of the investigation to support the clinician so that they can manage just like any other
- smear positive TB or proven histologically, TB. That's one another thing I'm quite curious
- to know because when you deal with cases with very difficult to get the diagnosis
- in terms of the laboratory, whether or not there's any work of a non-tuberculous
- mycobacterium because that's another differential of TB, which may not be
- supportive in because they might not be part of your work. There's another differential
- you might see if it doesn't fit into a laboratory diagnosis of TB. Thank you.
- Novel Njweipi Chegou: Yes. Thank you very much for those questions. So yes smear negative TB, that's
- one of the problems, challenges that we have. That's why I mentioned that the current TB, test
- reliance on we have very paucibacillary TB that doesn't show up as positive in
- the current test that we're using. So what we're hoping is that these biomarker based
- approaches that we are trying to develop, we think that's a target. That's something,
- those are the tools that we think will help with that. Now you're looking at material that is,
- you're looking at the host immune response against TB, not looking at the pathogen itself. We think
- that would be a nice indirect way of identifying, knowing that the patient is infected, that the
- patient has TB and not, you're not just treating the patient empirically as is commonly done now.
- Then the other thing, the other question that you asked, I cannot remember the
- second question was about non TB. Okay, yes. So a lot of the tests that we have now I know that
- like microscopy you cannot discriminate between TB and NTM with the microscope.
- If you do culture I think you should be able to do that. Again that is going to take you a long
- time before you get the results. So in terms of like the biomarkers that we're working on,
- it's about looking at specificity, right. Do they help in diagnosing ruling out patients who have
- TB like NTM. But NTM's are a problem in people with HIV right. I think that's one of the groups
- that you refer to is a problem in that kind of group. I think it will still be good to know that
- it's an NTM and not necessarily MTB that you are treating if it's posing a problem to the patient.
- Richard Catlow: Thanks. I think there was a question. Perhaps we can get the microphone.
- M4: My name is Mustafa. I'm from Sierra Leone and I'm studying biomedical science. Just like you've
- spoken regarding biomarkers, I was just wondering if there is any room to explain on multi-drug
- resistance of tuberculosis, because recently in my country there's research done that most
- of the drugs or the vaccines being used has been resistance on tuberculosis. I don't know if there
- is any explanation based on that, as has been the reason why there's a multi-drug resistance on TB.
- Novel Njweipi Chegou: Yes. So sorry to hear about your relative who is going through that. Yes,
- drug resistant problem. Drug resistant TB is a big problem, even in South Africa we have
- that as well. I'm not sure if I can comment on the reasons, all the reasons why we have
- drug resistance, but sometimes it's the person, when the person got diagnosed with TB started on
- treatment, but the person taking all the drugs at the same time every day. That's one thing
- that you need to look at. We need to take our medication faithfully. I know that from people
- who have been infected with TB, they say that the side effects are horrible. So you need really to
- make an effort to take the medication. So that's one of the reasons that drug resistance occurs.
- Again a person can be infected with a drug resistant strain from the start,
- and that is undoubtedly a big problem because that patient can't be treated with the normal
- TB drugs. Just wasting the time of that patient. That's one reason why we say we need tools that
- can help us to know whether TB treatment is the patient is responding to treatment early enough
- or not. So these are some of the things that will help in addressing those kind of issues.
- Richard Catlow: Thank you. High Commissioner. There's a question just behind you.
- M5: Okay. Can you hear me? No, no. I wanted to say, professor, thank you very much for this
- very impressive presentation. The figures you are giving us are a shocking,
- so many people dying a day and so many people dying a year or so on. Now, one question and
- I'm asking from a layman's point of view, I'm not a scientist. I think this question of mine
- is related to some of the questions that were asked here, why we continue to have this problem,
- which is killing so many people. I'm trying to compare with COVID, for example.
- We had COVID, but the whole world got involved and right now we're talking about almost this
- being eliminated. Yes, we can actually lift the restrictions and so on. Why aren't we
- pursuing this in the same vigour and energy in Africa and the whole world in general?
- Also I'm assuming these figures, and this is the second question, I'm assuming that these figures
- you are giving probably only relate to South Africa. Now, my understanding would be that
- there is no uniformity in terms of the some of the countries in Africa might even be worse off,
- if South Africa said to be having this level of development and so on, has this amount of
- deaths and so on. Now one can imagine deep down Africa then the problem is even very serious,
- which means Africa itself should have, maybe I should present this as a question.
- Do we have across Africa, the AU, for example, some kind of collaborative efforts to try and
- combat this problem, continentally, because if you are maybe succeeding in South Africa
- to do something, one would imagine that you would want to do that vigorously in the rest of Africa.
- Novel Njweipi Chegou: Yes. Thank you so much. These are very valid questions. So
- the issue about the lack of tools for TB, it's something that I try to comment on because if
- you look at COVID everybody was onboard. Everybody put the money into it. So really
- the issue is money. We need more funding. We have very smart scientists who are working on
- TB. Some of them actually love TB, to work on COVID to help address the COVID issue. I think
- enough motivation to put more resources towards TB, the TB problem, I think we can solve it. We
- should be able to solve it. Yes, it's just about us. So it's just about advocating
- more for more resources to be pumped towards developing tools to help us to control TB.
- I know that there are a few high level meetings that are planned
- towards the end of this year. We're waiting to see what comes out of those meetings by the nations,
- see what the nations are going to commit to in terms of funding TB research.
- Then when you talk about the like other African countries. Yes, if you look at a
- lot of the studies that I showed you, like you can still see this one, like
- screen TB, TBC, even this NIH funded study that were involved and these are studies that involve
- sites across Africa. Because of the limited amount of funds that we get for this kind of research,
- we can't include all countries. So we are limited to working with which two countries
- can we work with? Then you just pick two partners in one partner in one country,
- one partner in another country that you work with. So one thing that you said, which is very true,
- which is something I also believe in, which I've also commented on before, is that
- we may be underreporting the TB in other countries. Yes, in South Africa we know
- that nearly 60000 people die of TB every year. In other countries, if you cannot test for it,
- if you cannot test well for the disease, if you have only one laboratory across the country that
- is able to do confirmatory test for TB, how do you know? So we may be underreporting the
- problem. So and that is something that we don't have, I will not have an answer to.
- Yes but I think you are right. We may be underreporting in those countries because
- if we don't have the test in a way, how do you know that you don't have it?
- Richard Catlow: Right. There's a question here. Then we'll take one online.
- F1:
- Thank you for the very informative talk on the biomarkers and if we are to talk about
- the vaccines. So the BCG is the most talked about, talked vaccine that comes up when we talk about
- TB. As per my recent reading I also read about the VPM1002 vaccine. So if you were asked to comment
- on the immunogenicity and safety of VPM1002 as compared to BCG, what would be your take on it?
- Novel Njweipi Chegou: Yes, I think from the limited knowledge that I have, because I think
- I've been alerted to the immunogenicity was tested in our lab too. Though I was not heavily involved
- in that project. I think we're seeing the right things that we need to see with VPM1002. So it's
- one of those candidate vaccines that we're hoping that it will really make a difference
- in the control of TB, or at least improve on what we're seeing compared to BCG. So really
- I can't really comment more than that because I know that there are Phase 3 trials that are
- planned to start. Have they even started? Have they started already? Either they have started
- or they're about to start. So we have to wait and see what we get, the results that we get
- from those trials to see what difference the vaccine is making compared to BCG.
- Richard Catlow: Thanks. Now I think we have questions online which are going to be read out.
- M5: Yes, is from Jay.
- How do immune system triggered biomarkers show up in HIV positive patients?
- NC: How do the immune system trigger biomarkers in HIV positive patients?
- M5: How do they show up?
- NC: Yes, it's the same it's the same immune system. I always tell people that
- when we talk about different diseases TB, cancer and we're talking about immune system, sometimes
- we make as if it's the same immune system. A T-cell is a T-cell, a neutrophil is a neutrophil,
- and macrophage is a macrophage. So the same cells that respond when TB infects somebody are the same
- kind of cells that are going to respond, although in a different way to the other pathogens. So
- it's exactly the same thing. Pathogen comes in, the immune system tries to kill the pathogen.
- They try to bombard, produce all these biomarkers that are secreted. In the end, at times the immune
- system cannot kill that pathogen. Then it just ends up living, kind of living together. I can't
- kill you, but let's find a way to live together. Really, that's what happens most of the time.
- NC: Thanks. Is there another question online?
- M5: One more from Susan Grafe. Could a graded COVID type of test be used
- for different types of TB? They also thank you for the useful presentation.
- Novel Njweipi Chegou: Yes absolutely. Yes. That's what we're hoping to do. If you look
- at this test that I showed for COVID, that's exactly the kind of thing that
- we're trying to develop for TB you know. So yes, definitely that's where we are going to.
- NC: Good. Thanks I think we can take one more question if there is one.
- Yes, this final question.
- F2: Hi. Thank you for the talk. I just had one quick question or I guess a comment on
- when we're comparing TB to Covid, for example.
- I think a lot of the challenges that you've mentioned are very valid. I was just wondering
- how far can we really compare the two because of how different the transmission of COVID is in,
- you've got a chronic infection, you've got the chronic infection, which is TB, whereas COVID
- is generally more of an acute infection. Whether those differences are something which are being
- considered when we're comparing the two and the development of a test that's similar to COVID.
- Novel Njweipi Chegou: Okay, yes. Thank you for your question. I think the comparison that I
- made to COVID was in response to, with respect to the pace at which tools were developed.
- That's exactly what I was referring to. I know that they're different.
- TB is a very nice, clever bacteria. It doesn't kill you, it prefers to stay with you. It benefits
- from you, it's from you. Why should it kill? COVID kills you more rapidly! So but the point I was
- referring to more was about the pace at which the world got into making tools for COVID compared to
- TB that we've known is a problem for thousands of years. Then the very tools, same tools that were
- developed for COVID within two years or within a year even are things that we're struggling
- for all these thousands of years to develop for TB. So yes, can we, now that we've done COVID,
- can we shift start focusing on things like TB? That is where I was trying to get to.
- Richard Catlow: I think the problem was that TB has been with us for thousands of years,
- and COVID was a new crisis. I'm sure there could be plenty more questions and I hope you
- realise from the questions I stimulating we've all found the evening to be. But let us thank again,
- Professor Chegou, for this marvellous lecture. Before we finish, I would like to make the formal
- presentation of the Royal Society Africa Prize, and it's awarded to, as you know,
- to Professor Chegou for his work in the fields of pulmonary and extrapulmonary tuberculosis and his
- innovative project proposal. So let me formally present you with the prize. Congratulations.
- Novel Njweipi Chegou: Thank you.
- Richard Catlow: Thanks, and you
- get a scroll as well. So congratulations again. Well,
- let us now conclude by again by thanking Novel for this marvellous evening. Could I thank you
- also all for coming. I trust you've enjoyed and found hugely informative the lecture as I have.
- Special thanks, High Commissioner to you for joining us this evening. So thanks very much.
The Africa Prize Lecture 2022 is given by Professor Novel Njweipi Chegou.
According to the American Centres for Disease Control and Prevention, tuberculosis has been affecting humanity for over 9000 years. The bacterium that causes the disease might have been in existence for over 3 million years. Although curable, this disease that has over the years been referred to as “the white plaque”, “consumption”, “the captain of all these men of death” amongst others, currently still ranks as a top single infectious killer, killing more people than HIV/AIDs. Over 10 million people fell ill with tuberculosis in 2021 and about 1.6 million died, majority of whom were in low- and middle-income countries. In this talk, Professor Chegou will discuss the challenges that are involved in the control of tuberculosis, the need for new tools that may assist in the control of the disease, and the contribution that laboratories such as his, that are situated in high burden African countries, are making in the fight against the disease.
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