Podcast: Sickle cell disease

We speak with Dr. Nick Kassebaum, Dr. Theresa McHugh, and Azalea Thomson about their recent research analyzing the past 21 years of data on sickle cell disease.

Key takeaways:

• Despite being considered a “rare” disease, sickle cell affects a huge number of people in some parts of the world, like Africa and South Asia. 
  • In parts of West Africa, like Nigeria and Ghana, it can affect up to 2% of births. 
  • Nearly 8 million people were living with sickle cell disease in 2021.
• A person with sickle cell disease is also more likely to die from diseases that are common in these regions, like diarrhea, pneumonia, and malaria.
• What are the policy recommendations to improve sickle cell outcomes?
  • Improve screening systems for newborns, so parents are aware that their children are more vulnerable to common illnesses.
  • Increase access to drugs like hydroxyurea that can treat sickle cell disease.
  • Address elements of structural racism that have led to less funding and fewer options for treatment, compared to other similar genetic diseases. 

Read the research

This transcript has been lightly edited for clarity.

PAULINE CHIOU: Welcome to Global Health Insights, a podcast about the pressing health issues of today. I’m Pauline Chiou in media relations at the Institute for Health Metrics and Evaluation, or IHME. In this episode, we’re speaking about sickle cell disease, a hereditary disease that 8 million people live with globally. And we have new research out by the research team of Dr. Nick Kassebaum, corresponding author and adjunct associate professor at IHME, and Azalea Thomson, first author of the paper and an IHME researcher on the neonatal and child health team, as well as Dr. Theresa McHugh, scientific writer at IHME, who focuses on neonatal and child health. 

So thank you so much, all of you, for being here. You’re part of the research team that has just published the past 21 years of data on sickle cell disease that’s now in The Lancet Haematology journal. So, congratulations and thank you for being with us. Dr. Kassebaum, let me start with you. Before we jump into the research, explain to us what sickle cell disease is, and who’s most impacted by it.

DR. NICK KASSEBAUM: Sickle cell disease is, as you’re referring to, a genetic disease. So there’s one copy of a gene that encodes a protein that goes on to form hemoglobin. And if there is an alteration in that protein on both of the genes, then someone has what’s called sickle cell disease, that means their red blood cells carry oxygen differently. They deliver oxygen to the tissues differently.

And when someone is really stressed from an infection or high heat or some sort of illness, then those cells can actually form a sickle shape. They become sticky and then they clog capillaries. And so it can lead to things like heart attacks and strokes and really, really bad pain when the blood flow is cut off to a certain part of the body.

PAULINE CHIOU: And as we talked about, this is a hereditary disease. So who’s most impacted by it? 

DR. NICK KASSEBAUM: The gene was thought to arise in areas of the world where malaria has been endemic. Malaria has been present for hundreds, if not thousands of years. And so one copy of the gene is protective against malaria, whereas two copies are really, really harmful.

The places of the world that have most historically had malaria are places in Africa, most notably, some in South Asia, some in the Middle East and North Africa, in the Mediterranean region. 

PAULINE CHIOU: So you set the stage on what the disease is and where we see its prevalence around the world. You looked at global data from 2000 to 2021 in this systematic analysis of sickle cell disease.

What were the main takeaways, the main discoveries from your research? 

DR. NICK KASSEBAUM: The biggest takeaway from the research is how common and how pervasive and how big of a deal sickle cell actually is in many populations if you take account of its full impact. So many genetic diseases are certainly devastating for the people who have them and their families and communities who support them.

But they’re also often considered to be uncommon. In many places, sickle cell is not uncommon at all. Sickle cell disease can affect 1% to 2% of births in parts of West Africa, like Nigeria and Ghana. That’s an enormous number of people. And when we look at the things that people with sickle cell die from, it’s also the most common causes of illness in many of those parts of the world.

So things like diarrhea, pneumonia, malaria. And what we’ve done is bring all of that information together and try to triangulate, to understand, try to get a better understanding of how big the burden is. And when we do that, when we compare the outputs of that approach with just looking at who is known to have sickle cell and who was clearly identified to be in that category, there’s a huge gap.

So it might be 20 times or 40 times larger mortality if we look at all of those associated causes of sickle cell death as opposed to just those who are coded.  

PAULINE CHIOU: And if we read your research paper, let me bring Azalea into the conversation. When we read the research paper, the term that’s used is total mortality burden of sickle cell disease, which encompasses the secondary illnesses that Dr. Kassebaum had just mentioned.

And you found that sickle cell disease is a leading cause of death in different age groups from under-5 to 5–14 and adults 15–49. So, Azalea, that’s a huge demographic. Can you flesh out what's what this means? 

AZALEA THOMSON: Yeah. So to build upon what Dr. Kassebaum is speaking about, the problem and I guess the challenge in properly understanding the true mortality burden of sickle cell disease is that there’s a lack of data, a lack of studies that specifically measure that mortality, particularly in regions of the world where that burden is the highest, like Dr. Kassebaum said earlier, in sub-Saharan Africa and South Asia.

And so without a diagnosis at birth, which is relatively uncommon, unless there is a newborn screening system set up, without that diagnosis, a child might be more likely to go on to not receive appropriate prevention. So they might contract an infection or they might have a stroke, and then the doctor, because they’ve never been diagnosed with sickle cell disease, wouldn’t know that actually the true cause of their death, while it was perhaps stroke, what caused that stroke was sickle cell disease. 

And so that wouldn’t even be listed on the death certificate. So our study attempted to make a more accurate estimation of that true mortality burden, given the data scarcity and the known under-attribution of deaths to sickle cell disease. So, yeah, that was our approach there.

PAULINE CHIOU: So Azalea, how common are sickle cell births? And you spoke about the data gap, but how common is it and is it more common in certain regions than others? 

AZALEA THOMSON: Sickle cell disease is often called a rare blood disorder, but it is something that nearly 8 million people are living with, or in 2021 that was our estimated number, and I believe over half a million babies were born with sickle cell disease in 2021.

So that’s not a small number. And in places like Nigeria, Burkina Faso, Equatorial Guinea, those numbers are a lot higher than other parts of the world. And so, yeah, it’s definitely a rare disease in some places, but like Dr. Kassebaum said earlier, it’s really relatively common in other places. 

PAULINE CHIOU: And Theresa, I want to bring you into the conversation as well, because you also have been deeply involved in neonatal and children’s health.

The paper talks about the role of structural racism in access and in early treatment. Can you help us understand where that plays a role in this? And is it more so in certain countries than other countries? 

DR. THERESA McHUGH: Sure. Thank you for the question, Pauline. The impact of structural racism and discrimination on sickle cell disease is really far-reaching. There have been disparities in research funding for sickle cell disease compared to similar genetic conditions like cystic fibrosis.

Some have attributed the discrepancies in this funding distribution to the fact that the people primarily affected by cystic fibrosis are White individuals, while the majority of people who are largely impacted by sickle cell disease are of African descent. And so given this funding scenario and constraints with funding, there is a notable lack of medical advancements and treatments that are available for sickle cell disease.

PAULINE CHIOU: So as a result, is that the main challenge in getting awareness and access to treatment? 

DR. THERESA McHUGH: It definitely is a challenge. Nick and Azalea might be more equipped to comment on whether it is the major challenge, but it certainly is a limitation when there’s not a variety of options available for treatment. Then there will also be limited access to treatment, given that there’s a range of financial aspects to drugs that are available.

PAULINE CHIOU: Dr. Kassebaum, let me lob that question over to you. In terms of challenges, Dr. McHugh mentioned that structural racism could be one of them, maybe not the main challenge, but what are your thoughts about the challenges in terms of getting better access and treatment? 

Dr. NICK KASSEBAUM: So first and foremost, what Azalea was referring to, the most important thing to start with is diagnosis.
 
The United States is actually not alone, but relatively uncommon in the world is that we have a universal newborn screening where every baby born, regardless of self-identified race, is screened for a number of genetic conditions, including sickle cell. That system has been in place through the Senate since the 1970s and really got adopted in the 80s. 

So it’s pretty uncommon now in this country that someone born here doesn’t know that they have sickle cell disease or sickle cell trait. So if a mother or father has a baby with sickle cell, then they will know that the moment that baby gets a sniffle or gets a little bit of diarrhea, they need to go to the doctor. They’re not going to wait for three or four days until maybe they get over it because they know that their child is vulnerable and three or four days may be a really big deal.

One of the aspects there is about getting newborn screening to be much more common. It’s not universal because just knowing is an intervention. But for the funding mechanisms that are in place will require political will, they will require investments. And so some aspect of the lack of newborn screening programs worldwide is a reflection of in some places it’s going to be potentially simply resources, whereas in others that may be a reflection of prioritization away from a disease that affects primarily Black people and those of South Asian descent.

This is also a separate question from the treatment. So, we look at the major medical advances that have happened over the last half century in cancer and other blood disorders, in the treatment of cystic fibrosis, of muscular dystrophy, of a number of different conditions, and really there haven’t been all that many new therapies developed for sickle cell and there hasn’t been a whole lot of advancement in either our understanding or our approach.

Gene therapy is certainly tempting and maybe holds some promise, but that’s about it. And I can’t help but think that that also is a reflection of the political will and the prioritization, not reflecting a disease, not prioritizing a disease that affects primarily people of African and South Asian descent. 

PAULINE CHIOU: Well, the research paper certainly lays out the dire situation, especially as you’re expecting to see the number of cases of sickle cell disease increase and, Azalea, as you project ahead, you’re expecting an increase, especially in South Asia and sub-Saharan Africa.

If you had the ear of policymakers, knowing that the number of cases will increase, what would you say the best solutions are? 

AZALEA THOMSON: First, I think a priority would definitely be making sure that sickle cell disease is on the government agenda, that it’s incorporated into the overall public health system that the health ministry is set for and beyond, making it a priority, especially in the places where we know there are a lot of cases.

It’s also super important to make sure that there’s the financial backing for that. And so getting it on the agenda, making sure there’s funding, and having positive financial and educational reinforcement from NGOs, from the private sector, even from the media. I think in a lot of places, being able to have a local champion who will say this is really important.

We need to designate our attention and our funds toward this is really important and I think it’s not like we don’t have tools or we don’t have treatments for sickle cell disease. There’s a simple point of care test which can be used in rural parts of the world so that you don’t need to go to a hospital in order to get diagnosed.

You can just do a simple blood spot test with these devices, and that can help do a lot more widespread testing. That’s already been done in places like Nigeria.

PAULINE CHIOU: That would be effective. Excuse me for interrupting. In rural areas where access to a facility might be difficult. 

AZALEA THOMSON: Yeah, definitely. And I think finally, I would just add hydroxyurea is one of the most effective, safe drugs to treat sickle cell disease, but it can still be hard to access and there’s always a factor of cost.

And so trying to make efforts in the policy direction to make that drug more accessible and that health care providers are more educated and aware of how to prescribe that drug, I think those are all steps in the right direction. 

PAULINE CHIOU: Dr. Kassebaum, when we look at this from a global perspective, there was a list of countries in the research paper that really stood out, because when you take the total mortality burden and take into account all those secondary illnesses that sickle cell disease can cause, sickle cell disease becomes among the top three causes of death in Jamaica, Portugal, Oman, Libya, and San Marino.

And when you look at that on paper, you sort of scratch your head and say, what is that about? Because these are very different countries, different income levels. So can you speak to that about why this is a global issue? 

DR. NICK KASSEBAUM: Certainly, as you talked about a little while ago, the origins, evolutionary origins of sickle cell disease are related to where malaria may have been for thousands of years. But people have spread out through the world also for thousands of years.

So our genetic origins may have been there. Now there’s a migration to different places, so there are very few places that are not in some way affected by sickle cell. We look at certain countries that have really high rates of sickle cell disease. They also have a history of being colonized by certain countries in Western Europe, Portugal, Spain, the UK, France, all have the significant colonial presences in Africa and maintain, even after independence to all those countries, pretty close ties economically and education-wise.

And then there’s a lot of people going back and forth. I expect in the case of some, like Portugal, that’s largely driven by migration. And I would say that recent migration patterns from Africa also suggest that there may be poised to be increases in many European countries in the coming years, including potentially some European countries that have not historically been the destination for migrants leaving Africa.

I was also going to mention Jamaica is a really important example, too, because Jamaica is probably a shining example of a middle-income country – so not low-income, but not incredibly high resources – that long ago recognized that sickle cell is a really major problem. And so they’ve had in Jamaica a national sickle cell strategy since at least the 1990s.

And with this universal screening, they’ve developed a lot of research capacity and being able to understand what happens, what are the other risk factors for people with sickle cell? Tons of publications, tons of what we know about sickle cell in Black people is from these studies in Jamaica. And so that’s a great example for others to try to follow and emulate.

PAULINE CHIOU: So, Jamaica’s is a success story on this issue. Dr. McHugh, following up on what Dr. Kassebaum was saying in terms of migration and where sickle cell disease can surface, if we are expecting this to become more of a problem in certain countries, what are your thoughts on the stress that this could cause in terms of health systems and access to care in some of these countries that may not right now be prepared for it?

DR. THERESA McHUGH: It is a tricky situation indeed, because even in high-income countries like the United States, sickle cell disease patients experience challenges with health care access and health care quality. And so even though we technically should be prepared to treat and maintain a high quality of life for individuals with sickle cell disease, that unfortunately is not always the case.

So it was mentioned earlier that a common manifestation of this disease is pain, and pain can only be reported by the individual who is experiencing it. So it’s too often an occurrence, but we’re finding that sickle cell disease patients will be racially profiled in the clinical setting as being drug seeking and can have their pain discredited by a health care provider.

And so these negative experiences that are encountered in the health care setting, combined with other factors as well, have led to a distrust of the health care system within the sickle cell disease community.

PAULINE CHIOU: So your research has really lit a fire on discussions of many different aspects, from the social aspect to the research angle to the angle of access as well.

Thank you all so much for being part of this discussion, Dr. Nick Kassebaum, Dr. Theresa McHugh, and Azalea Thomson, we really appreciate it.