Latest / EHA Unplugged / Point-of-care Tests for Neonatal Screening of Sickle Cell Disease (with Prof Béatrice Gulbis)

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Point-of-care Tests for Neonatal Screening of Sickle Cell Disease (with Prof Béatrice Gulbis) · EHA Unplugged

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  My first recommendation is that we have to do newborn screening
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  and so we have to use the devices that are the best fits
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  your context. And if the context needs
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  something really simple, simple user friendly, you have the
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  results at bedside directly, so it's easier to be sure that you
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  can enter the any patient affected by the disease into the
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  the patient journey care do it. Welcome to EHA Unplugged, the
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  official podcast channel of the European Hematology Association
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  EHA. I am your host, Isabella Libre,
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  and today we have the pleasure to have with us Professor
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  Beatrice Guldbis. Professor Guldbis is part of the
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  Department of the Centre of Human Genetics from the Hospital
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  Universitar de Bruxelle. She's also the Co coordinator of
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  Euroblog Net, the Europeans reference network for rare
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  hematological diseases. There she contributes with her
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  expertise in genetic counseling and neonatal screening.
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  Thank you for being with us today.
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  Thank you for having invited me to this podcast.
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  Thank you very much. So today we will be discussing
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  her recent work on point of care tests for neonatal screening on
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  sickle cell disease. And we will have first an
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  overview of what sickle cell disease is, the type of
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  mutations that lead to this. We will discuss the current
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  testing technologies for sickle cell disease and also what the
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  future is and how can this be implemented.
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  So my first question is what is sickle cell disease?
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  What mutations lead to this? So of course it seems really
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  easy to know that only one mutation in the beta globin gene
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  can conduct to the fact that there is cycling within the red
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  blood cells. And the abnormal hemoglobin that
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  is related to this mutation is the S hemoglobin.
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  And when you are homozygous for it, you have the cycling, which
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  is a polymerization of the hemoglobin within the red, the
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  red blood cell. But in fact, we have learned
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  that it's much more complicated than this.
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  There are many systems. So we know that other gene
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  modifier can be encountered and that that will work on the
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  expression of the disease. One of them is related to the
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  possibility to produce the fetal hemoglobin after birth.
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  Otherwise, it decrease and it almost disappear.
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  And we have learned a lot about the complexity of the expression
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  of the fetal hemoglobin. And thanks to our researchers,
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  it has been also applied for new therapies like Genes therapies.
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  So why is it important to screen newborn babies for sickle cell
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  disease? First of all, I think that all
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  of us, we would like to have a diagnosis even if we don't have
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  a treatment. So the the first thing maybe but
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  of course at in many countries new one screening at has been
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  implemented at a national level. And the first pilot was done in
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  1976 in New York on cold bloods. And almost 10 years after, there
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  was a randomized trial that demonstrated that prevention by
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  oral penicillin is a gives a great benefit against infection,
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  which is the first clinical complication that might conduct
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  to death. So the randomised trial was
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  stopped earlier because they saw this impressive benefit of the
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  oral penicillin. And then one year later, the NIH
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  declared that newborn screening had to be recommended because
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  you need the diagnosis to apply the prevention.
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  And of course, if you make the newborn screening, just keep in
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  mind that you don't have just to do the diagnosis, you have to
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  enter the patient into a patient care journey, a comprehensive
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  care. Otherwise you'd you have only
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  epidemiological data, but you you don't prevent any
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  complications. What is the prevalence of sickle
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  cell disease in Europe? We know that in Europe it's
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  still a rare disease. When you have the definition of
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  rare disease by the European Commission and the European
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  level, we know it's less than one baby for 2000 births.
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  So it's it's really a few babies.
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  But if you go to sub-Saharan Africa, the highest birth
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  prevalence is in Nigeria. You have around 100,000 babies
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  born every year. So that's a lot.
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  So the the figures are quite different from one region to
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  another. What is the normal test in
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  Europe and is it the same in this regions?
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  What has been implemented in the European countries where is the
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  highest prevalence at birth? They implemented the second cell
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  screening at births within the national screening for inborn
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  errors like phenylketonuria or hyposteroidity.
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  And of course in many European countries where the level of
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  birth prevalence is really low, there is nothing done or there
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  is only screening of families who are at risk to having a baby
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  affected by the disease. While if you look in in
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  sub-Saharan Africa, the picture is totally different, the
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  coverage of the the screening is only related to pilot studies.
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  Still today all the coverage is less than 50 persons.
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  And the other great difference when you compare it to Europe,
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  it has been demonstrated by the newborn screening society that's
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  in this in 70% of the the the countries in sub-Saharan Africa,
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  the only disease that is detected at birth is sickle cell
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  disease, but not the other disease like phenylketonuria or
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  hypothyroidism. And in my experience, what I saw
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  often is the fact that pilots or coverage are related to big
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  cities and not in the remote areas.
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  So this means that you have to think about a way to be sure
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  that you can reach those patients somewhere else.
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  The other experience that I have when we we implemented newborn
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  screening, sometimes you lose the baby, you have to diagnosis,
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  but you can't catch the family and enter the, the child within
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  a comprehensive healthcare. And this is really a, a, a
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  problem. So we have to think about both
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  things. How can we make the diagnosis
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  and do have a 100% coverage and the at the other hand how can we
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  be sure that we can take care of those babies?
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  So now talking about this point of care testing technologies,
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  yeah, that you have been developing, can you explain what
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  they are and what is the purpose of this point of care testing?
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  We have been able to introduce innovation and related to
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  miniaturization. So if you have immunosis, what
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  means immunosis is the fact that you have an antigen, this is the
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  hemoglobin S for example, and you have an antibody and then
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  you can make a color with a band.
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  So you you can put it in a very small device.
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  You don't need a power supply. It's really robust against
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  humidity and high level of temperature and everything.
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  So it's something really easy. It's also something that can be
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  done that can be performed by a nurse, by a physician.
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  So someone with without the background of a lab technician.
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  And This is why you can, you can think about to use it in remote
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  areas. The cost is relatively low, but
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  of course low. What does it means if your
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  income is let's say $5.00 a month?
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  So you have been in the lab that has developed this test?
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  We have tested those devices. OK.
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  In the past we were using isoelectric focusing and then
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  the evolution was with more sophisticated technique, if I
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  can say it's chromatography and also capillary electrophoresis.
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  We compared all those point of care testing with those
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  conventional techniques. So we compared one of the first
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  point of care testing that was available on the market more
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  than 10 years ago in, in, in my lab.
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  And then as I told you, our team work a lot with our colleagues
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  from Burkina Faso, from Mali, from Republic Democratic of
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  Congo and we have been working to together to test those
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  devices locally. How successful are these devices
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  in these countries? Have you been able to use them
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  widely? If you look at the healthcare
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  system in sub-Saharan Africa, of course you have central lab and
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  most often in big cities, but then you have different level
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  and you go at the end in small centres where even the the
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  physician goes there once a week for example.
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  So you have to, to be sure that you can use a device over there
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  without any training and you are confident with the results.
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  So this means that for most of the patient, let's say if you
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  have a a normal results or no hemoglobin S, you won't test
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  anymore and you can tell the family or the patient that that
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  everything is OK. So comparing then this point of
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  care test to the conventional methods, how reliable are they?
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  For, for what we need, they are reliable, but I, I think that we
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  have always to test it locally to be sure that we don't need a
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  control. So the, the confidential
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  confidentiality that you have with the test is, is good, but
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  you have to relate it it to your population.
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  Let's see. So when you have a sickle cell
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  disease, you might be homozygous for hemoglobin S, you might be a
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  compounded erozygous for hemoglobin S&C and and so on.
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  The population that you test, maybe it's a child or an adult.
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  So the level of hemoglobin S is very high while when you are on
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  your bone screening the level of hemoglobin S might be very low.
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  So you have to know the context and with the context you have
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  really to test the feasibility and how how you are confident
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  with it. So this means do you have false
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  positive or false negative results?
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  So is there interference with fetal hemoglobin with in newborn
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  babies? So it depends on the point of
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  care testing that you you use. So if you use the immunoresis,
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  you don't, you don't look at the fetal hemoglobin and there is no
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  interference with it. If you have another test which
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  is related to electrophoresis, you might have an interference
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  with it, we call it smear. You might have a large bands of
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  fetal hemoglobin and it can overlap the band of hemoglobin
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  S, so sometimes it's a little bit tricky.
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  But with the system with electrophoresis, there is an
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  added device that is related to artificial intelligence.
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  So with the device, this device, there is an interpretation.
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  So you don't need that the nurse or the any technician in the
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  healthcare system interpret the test.
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  It is done by the by the system, by the device.
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  And it's a nice device because it's you can move it anywhere.
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  So you need minimal training, yeah.
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  And you can implement it then in very simple settings, let's say.
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  Yes, indeed. Is this the only device of this
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  kind at the moment? So there are many, many, many
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  different techniques have been developed related to RNA,
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  related to DNA, but many, many of those new techniques were not
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  studied extensively. So they are still not available
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  also on the market. I wanted to add something, a
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  group in sub-Saharan Africa, it's a Cycling Africa consortium
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  and they, they just published a paper in this year.
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  And it is really a nicely explained the fact that when you
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  want to implement point of great testing, you need the approval
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  of the families. So they're working on New World
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  screening. So the families have to
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  understand why we do this, is it safe?
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  And then you have to be sure that the the, the individuals
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  who will perform the tests are also involved.
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  They understand that is it is for the benefit of the patients.
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  Then you have to be confident with the test by itself.
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  But there are also something very important, it's
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  sustainability. So they involved also the
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  politician. So they described this overall
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  process and we hope that we will have the the results soon
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  because again, if you really want to implement the newborn
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  screening, but you can't do it for a long time and you can't
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  integrate the affected baby into the overall care.
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  It's a lost of, of, of money. So you have to involve the
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  stakeholders. So this paper is very nicely
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  written in the way that we understand the overall aspects
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  that you have to take into account to be sure that you will
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  have positive results. Are these tests also being
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  developed for other conditions? With those tests you can look at
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  the the fact that you have no hemoglobin A and no other
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  abnormal hemoglobin. So there is a clue that the baby
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  has is affected by beta thalassemia, but the newborn
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  screening has not been implemented for beta thalassemia
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  because there is no prevention that you can give.
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  OK. So it's it's not necessary, not
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  necessary to to have the diagnosis at at birth.
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  If you have to think about point of care testing, when I asked to
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  my colleague, do you use it? Do you use it?
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  It was never for newborn screening, but it was more when
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  you have a genetic counselling, for example, if the father is
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  there, often it's not so easy to have the the sample so you can
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  test it during the medical visit.
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  You can also test the the old family if they are there so the
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  other children. So this is one of the the use
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  that I've heard about, even if there is no publication about
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  it. So what would be your
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  recommendations for haematologist that are
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  considering to implement the use of this point of care SCD
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  testing technologies? My first recommendation is that
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  we have to do new board screening and so we have to use
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  the devices that are the the the best fits your context.
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  And if the context needs something really simple, simple
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  user friendly, you have the results at bedside directly, so
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  it's easier to be sure that you can enter the any patient
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  affected by the disease into the the patient journey care.
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  Do it if you want our audience to remember one thing from this
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  conversation. For what would it be?
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  I want to thank you to highlight this because I think that we, we
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  have to collaborate all over the world and to be aware that what
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  is your context might be not the context somewhere, somewhere
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  else. Yes.
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  Is there something else you would like to say that I have
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  not asked and that it's important to highlight?
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  Maybe when when you think about point of care testing, I think
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  that's what is important to have in mind is the fact that you
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  bypass several steps. This means that when you you
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  take the sample, you don't have to transport the sample.
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  So you gain time. Then you have a test and you
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  have directly the patient or the family facing you and you can
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  show the results. If you see a band, you see
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  something. It's like you remember when we
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  were during the COVID-19 periods, we test ourselves to
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  be, to know if we, we, we were contaminated and could we invite
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  our family or, or friends or whatever.
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  And do you have to take the blood?
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  It's a finger prick, or for the baby, it's a hill.
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  Prick. So it's as simple as a COVID
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  test, you would say, but you have to take the blood.
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  Like for the overall newborn screening and so you can put the
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  blood in a capillary or in a tube or even on the on the paper
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  and then you put it in in a buffer.
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  You just mix it, you wait a few minutes, then you put it on the
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  device and you let it go by capillarity and then the band
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  appears. Or when it's electrophoresis,
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  everything is in a microchip in a cottage and you wait for the
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  migration of the bands and you look at the bands.
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  So it's really easy and then you can show it to to your patients.
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  How long does it take? Overall, 10 to 15 minutes, you
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  know, when you think about point of care testing, it might be
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  self testing like like you, you, you, you said for COVID-19.
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  But here it's someone or, or make the, the sampling and who
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  do The Who do the tests. But you know, it has been
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  developed also, for example, for CRP, which is a protein related
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  to inflammation. And then the General
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  practitioner can use it just not to give antibiotics if it's not
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  necessary. So it's also a test that you can
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  do everywhere. So point of care testing has
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  been developed almost everywhere.
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  And in in the intensive care, what they wanted to do is to put
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  a device within a vein or an an artery so you can test
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  everything. So this is also point of care
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  testing. So thank you very much,
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  Professor Hugo Levis for being with us today.
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  Thank you very much to to you too.
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  It was a really a nice experience and if anyone would
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  like to have more information, of course they're.
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  Free to come. Thank you.
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  Yeah. Sure.
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  Thank you also to the audience for listening and please stay
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  tuned for more episodes.