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OmicsXchange Episode 14: Genomic Surveillance and Outbreak Response in Africa with Alan Christoffels


 

Angela Page 0:03  

Hello, and welcome to the OmicsXchange. I’m Angela Page. Today I’m speaking with Professor Alan Christoffels about the role of genomic surveillance and outbreak response in Africa. Alan is the director of the South African National Bioinformatics Institute based at the University of the Western Cape. He is also the director of the bioinformatics unit of the South African Medical Research Council. Alan’s lab builds computational tools for analyzing high throughput genomic data for infectious disease research. And he’s also the director of the Public Health Alliance for Genomic Epidemiology or PHA4GE and a member of the founding working group of H3Africa. And both PHA4GE and H3Africa are two really important partners for GA4GH. Welcome, Dr. Christoffels.

Alan Christoffels 0:46  

Thank you very much, it’s a real pleasure to be here. 

Angela Page 0:49  

Thank you.

Alright, so let’s get started. So, we talked at the beginning that your lab is focused on computational tools for analyzing genomic data. So, how does genomic surveillance play into outbreak response right now?

Alan Christoffels 1:02  

And I think, probably, it’s really good for the listeners to understand what we mean by genomic surveillance. So, when we think of using genetic sequencing of a pathogen like a virus, when we are wanting to understand the genetic variation within a pathogen, we are really using genomic sequencing technology to understand the basis of how pathogens are changing. And [to align] to that we [are] trying to understand the transmission of a specific infectious disease. And so I think using that as a backdrop, we see that it really starts with sequencing, in this case, your virus sample, speaking about SARS-CoV-2, and then really looking at how that virus mutates or it goes from one variant to another at one level. And then at another level, to understand how that data, when combined with epidemiological information, can shed light on transmission, so how the virus spreads from one person to another. 

And so with that information in hand, really what happens is that it then empowers your public health officials, to tailor-make calls to adjust a particular intervention. And it doesn’t have to be Covid-19, you could think of a — some bacterial resistance outbreak in a hospital ward. And you’re wanting to really understand how you isolated that particular infection. And so you see that these genomics surveillance techniques are really critical at the outset of wanting to control and also understand the dynamics of a disease outbreak. And I think maybe just to add to this, if one just looks back at some of the disease outbreaks on the African continent, you think of the 2013 to 2016 Ebola outbreak, what was critical in that period was an early identification of the pathogen and then understanding whether or not you’ve got cross border spreading of this disease or whether or not it was a disease that was localized to a particular country or area.

Angela Page 3:28  

In our email exchange leading up to this call, you said that there’s a separation between the African public health service community and academia, which limits knowledge transfer, and even data generation. So, can you talk a bit more about this? And why do you think this is the case? And how does it impact the public health response?

Alan Christoffels 3:46  

When you do have a disease outbreak, you really look to a National Public Health Institute in order to provide the guidance, and also the directions in moving forward. What we are clearly seeing is that a lot of the technical skill, and I just use genomic surveillance as an example, the technical capability resides in part within the national public health departments. But there is a predominance of critical mass sitting within a university system. So that you find consortia like PHA4GE has really been an attempt to bring what has been academic bioinformatics development, more into the public health space, where you wanting to see the implementation of methods and technology that will then inform the public health response. And so what we are certainly finding as we engage more and more public health departments on the African continent, is that there appears to be a dearth of technical skill needed to carry out the type of genomic surveillance methodologies which we require. And so it provides actually a very good opportunity in order to try and align some of the skills development, which occurs within an academic space, but to align that, and focus more on the needs of the practitioners, the public health practitioners that in fact needs to carry out the kind of work that has to be done. 

And so I suppose what I’m really saying is that it is an ecosystem of an academic space, which I think we find valuable. Whereas if you go to the public health implementation space, I mean, it is really about taking technology and utilizing it. And so how do you then reward and recognize the growth, the advancement, the promotion of individuals in these two spaces, because at the public health practitioners space, the requirements, and the requirements of publication being linked to incentive funding, the funding might not be as strict as what we have in the university space. And so, therefore, I feel that as we look to ways in which we are going to support national public health responses globally, and in the context of the work that we’re doing, in the context of the African continent, we really need to see how do we empower national public health facilities, so that they have the wherewithal, in fact, to carry out the mandate? And I think that’s probably the current tension, which we are having is how do we make sure that what is an academic project of developing a data standard, for example, doesn’t just get left with the academic project and the publication that is produced, but we literally start to see its practical utilization within the field. And I think that is really where we need to be working.

Angela Page 7:19  

So on that, I mean, do you have ideas about how you might make that happen? How you can ensure that knowledge transfer?

Alan Christoffels 7:27  

Yes. So there [are a couple of things] that are currently underway. So maybe I just, again, draw on some of the PHA4GE work, there are working groups within PHA4GE, that are developing particular pipelines or particular data standards. And what we have done in the last five months, is to partner with ten organizations in both Africa and Southeast Asia, to really start to ask the questions, can we practically implement the data standards that are developing or that are developed within PHA4GE? Can we see those being utilized in the public health space? And so it’s not only utilizing them but to critically [assessing] whether or not these standards are useful? Because I think you might find that an implementation scientist might come to this project from the view and decide actually there are a number of variables or a number of considerations, which we have taken in an isolated space that actually is not relevant, or we are missing key variables that have to be included. And so I think this would be a way in which you have a partnership between both public health individuals, as well as bioinformatics scientists to really collectively consider what are the best tools that [need] to be developed with application in public health. And so that is certainly one example that we’ve been working on. And I think there are a myriad of training programs that have either been launched by people, including ourselves, that are being looked at ways in which you can start to ask public health officials, what are the specific training programs that you need in order to deliver on your mandate? And I think that is really where we are currently at.

Angela Page 9:42  

Yeah, I mean, certainly at GA4GH I think we take the perspective that having the end-users right there at the table, in the end, the development of the standards is critical. So that actually sounds like that’s sort of one of the approaches you’re taking it PHA4GE—and just to remind the listeners, PHA4GE is the Public Health Alliance for Genomic Epidemiology. So, you know, as a technical standards organization, we have to ask the question about standards. So you talked about aligning the intellectual communities and the public health and academic spaces. But what is the value of actually having technical alignment and having data standards and system standards that enable that technical alignment? And what impact will those standards have on the actual disease outbreak response?

Alan Christoffels 10:25  

I think that’s actually a critical question. So what we find is that if we use Covid-19, as an example, we find that many people are collecting biospecimens. So that would be nasal swabs, in this rush to ensure we can increase the throughput of our SARS-CoV-2 tests. But really, during a pandemic, or during a crisis, very little thought is given to exactly what needs to be collected. And so what we discover is that time and time again, when people are reflecting on a disease outbreak, there is always the comment, you know, we should have created this, we should have really asked for more of this. And so what we’ve really seen, even with the SARS-CoV-2 metadata standard that we have developed within PHA4GE, is that we’ve had multiple folks give input into the appropriate variables that are needed, some would be essential, some would be nice to have. But at least you’ve got this template that field workers can use when they are collecting information. And we have seen probably repeatedly that [in many] countries, there is such a lot a richness of data that is lost during crisis management, that having an agreement on a particular data standard, a particular format, really adds value down the line when we are trying to share data across borders, across continents, when you’re trying to aggregate information down the line. And so this for me, I think is a critically important step, when we have to ensure that we align our understanding of what would be the appropriate standards. And I’ll give you another example, my team was involved in assisting our National Institute of Communicable Diseases, with the sequencing and analysis of the first Sars-Cov-2 viral genomes from South Africa. And what was quite apparent during that period is what we needed was a specific manual, a specific standard operating procedure, that was readily accessible to the biology technicians, for isolating vital samples for enriching the viral sample against the backdrop of the host material, and then having the appropriate protocols in place for doing quality control of your sequenced sample. And so those kinds of readily available how-to manuals [become] something that is actually a critical factor when you [race] against time. And so this is where we are seeing with our training programs, when you build a skilled workforce within the public health space, it is important that we understand that the working environment must be such that we have an appreciation for the need for standardized, reproducible protocols, that we can then rely on the underlying data that gets produced. 

Angela Page 13:57  

So, thank you. That’s all really interesting. And I guess, as I’m listening to you talk, it sounds like, you know, a lot of the inconsistencies that you’re describing across the way that different labs are operating doesn’t necessarily just apply to Africa. It sounds like a kind of a global problem. And I’m curious how, you know, what, whether there are unique challenges within the continent that the global standards community is or is not, you know, currently meeting?

Alan Christoffels 14:27  

So, [I think that globally] we share similar challenges. The one thing if I could put a plug in here for GA4GH, I think the one project that has really been exciting for me to watch is your Data Use Ontologies. It is certainly a global challenge in trying to understand how do we develop approaches that will allow users to better understand the usage framework of data sets. And as we democratize DNA sequencing, we’re going to get this huge rush of data being produced. And we see and we are seeing it already. And so how do we identify technological methods that will aid in our ability to understand the framework that will allow us to use or not use certain data? Interesting, [these] examples are what is being attempted globally, will have a direct impact on some of the data governance challenges which we are currently having on the continent.

Angela Page 15:49  

So earlier, I mentioned that it might be interesting to discuss how learnings from Covid-19 could impact future pathogen response. Could you talk a bit about that now?

Alan Christoffels 16:00  

And so yeah, I think for me, if I were just to look back, and also some of the failings of our responses to previous outbreaks, I think what we’ve done correct, this time around, certainly on the African continent, is better coordinations. And so, back in 2017, we had [the establishment] of the Africa’s Center for Disease Control and Prevention, something akin to the US CDC, and it was that continental arm that really led the establishment of a range of task forces, which were really targeting a multi-country response. And I think that that certainly helped [us] see the establishment of what was the African Task Force on Coronavirus, preparedness and response. And that had a technical wing to it, which was looking at the provisioning of infrastructure, the provisioning of sample tracking, the moving of biospecimens to locations where they could be sequenced rapidly. And I think that has had an immense impact on our ability to monitor and to track. I think that is a big one, we look at a global response to the supply of vaccines. And although that topic has been marred by huge controversies, what we have certainly seen is the establishment of a network of an organization that could collectively have a stronger bargaining power in order to obtain cost-effective vaccines. Because I think if we were looking at future responses, I think it is acknowledging the role and the value of both regional coordination and that tied to global coordination productivities as well, I think that would be the big one.

Angela Page 18:22  

So to wrap things up, what are some of the limitations to achieving the level of genomic surveillance that’s needed for effective outbreak response?

Alan Christoffels 18:30  

So probably let me stop and say, if I look at what PHA4GE has been doing the last nearly two years, our focus has pretty much been driven by the current Covid-19 crisis, although that is not intended to be the only work that we are doing. And I personally would like to see some of the mycobacterium tuberculosis, much-needed data standards come through. When I look at GA4GH, historically, I’ve always seen that as an entity that responds to the needs of human genomics. However, I think that where we really have to apply our minds is how to [extrapolate] the work that we are doing to this interdisciplinary approach. We haven’t really seen and certainly, I haven’t really pushed it within PHA4GE. And I think probably not so much in GA4GH, how do we get folks in the agriculture sector to start to recognize the utility of what has been driven in one area that has got an absolute direct implication for the agriculture sector, for the veterinary sector, and little known bringing on board some of the environmental challenges. And so for me, I think, when we start talking about a phrase that you guys use in GA4GH, which I’ve started [using] quite a bit now for Driver Projects, is how do we look at Driver Projects that will be much more cross-cutting beyond our very narrow view of working either in the human space or in the pathogen space. But I do think that this is a space that we need to seriously look at. And I think it would bring together activities that are actually currently underway, that [probably] appear to be more separated, but they could very well be aligned. And I think that for me is going to be the space that I’d like to see both GA4GH, as well as PHA4GE, grow in.

Angela Page 20:52  

That is a great, I think a great point to end on. Alan, it’s been a pleasure talking with you today. Thank you so much for joining us.

Alan Christoffels 21:00  

Thank you. It was a pleasure.

Thank you for listening to the OmicsXchange, a podcast of the Global Alliance for Genomics and Health. The OmicsXchange podcast is produced by Connor Graham and Stephanie Li, with music created by Rishi Nag. GA4GH is the international standards organization for genomics aimed at accelerating human health through data sharing. I’m Angela Page, and this is the OmicsXchange.