Int Health 2014; 6: 269–270 doi:10.1093/inthealth/ihu045 Advance Access publication 6 July 2014
COMMENTARY
Addressing the global health burden of sickle cell disease Peter J. Carey* Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK
Received 1 April 2014; revised 13 June 2014; accepted 16 June 2014 A review of the clinical manifestations of sickle cell disease (SCD), available therapeutic interventions and a necessarily limited assessment of progress with their implementation in Nigeria (the country with the largest number of affected individuals worldwide) was recently published in this journal. Despite a disappointing dearth of targeted therapy for a condition whose molecular basis has been well understood for half a century, there is a wealth of evidence-based supportive interventions, including antibiotic and vaccination prophylaxis against early bacteraemic mortality, childhood stroke risk prevention, patient and population education and screening and community care provision that are simple and inexpensive to implement. There is a real opportunity for international collaboration to drive an improvement in healthcare provision for this condition. Keywords: Health resources, Hydroxyurea, International health problems, Sickle cell disease
Introduction In their article in International Health on the evolving medical services for sickle cell diseases (SCD) in Nigeria,1 the authors set out an excellent review of the effects of the sickling haemoglobinopathies and the available interventions. Progress with the implementation of these interventions in the country with the largest number of affected individuals worldwide was assessed by a questionnaire survey of a limited number of sickle cell centres. It is salutary to reflect, in this era of molecular diagnosis, that we have come to expect the regular and numerous pharmacological developments of effective targeted therapies for many haematological malignancies. Yet, 50 years since the molecular coding and structural abnormalities in SCD were fully described, there is a dearth of specific treatments for these conditions. The most applicable interventions are indirect and supportive, though potential strategies for prevention have been informed by molecular understanding.
Specific therapy As far as specific therapies are concerned, there is haemopoietic stem cell transplantation, red cell transfusion therapy and hydroxyurea (HU) (hydroxycarbamide). Haemopoietic stem cell transplantation remains the only potentially curative option. Despite the huge complexity and expense that is always going to restrict its availability, it is still a rather blunt instrument fraught with morbidity and mortality. Chronic transfusion therapy, even when available, is complicated by problems related to iron overload, chelation, alloimmunisation and venous access issues. In countries like Nigeria where transfusion services rely heavily
on family donors, the difficulty in SCD is that blood from individuals with sickle cell trait (or of course with the disease itself) is not suitable, which precludes donation by the majority of siblings and parents. The accidental discovery of the beneficial effects of HU on the incidence of complications in SCD is important in terms of its potential wider applicability, with the availability of regular blood counts and patient and healthcare provider education, the only barriers to safer implementation on a wider scale. Childhood stroke has been a major disease burden in SCD patients surviving infancy. A potential childhood intervention in SCD follows the demonstration of the preventive effects of chronic transfusion for stroke risk, and the ability to identify at-risk individuals by ultrasonic transcranial Doppler (TCD) screening.2 The implementation of TCD screening programmes has been a major focus in western countries. There has been little point in doing so in countries where the required transfusion therapy is not then going to be available for the individuals identified. The work on stroke risk prevention with transfusion was undertaken before the beneficial effects of HU in SCD were recognised. There is an urgent need for evidence on the potential effect of HU in this area and whether or not it might be comparable with that of transfusion. There are anectodal suggestions that HU may be at least partially effective,3 and if this were demonstrable the prospects of achievable access to an effective intervention are much more realistic. The proposed Stroke Prevention in Nigeria (SPIN) trial,4 though not directly comparing the two interventions, is ideally placed to address the question of whether there is an important HU effect and the international sickle community will await its outcome with great interest. Wider implementation of HU therapy would be challenging, but more readily achievable than chronic transfusion therapy.
# The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: [email protected].
269
Downloaded from http://inthealth.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 23, 2015
*Corresponding author: Tel: +44 191 282 4743; E-mail: [email protected]
P. J. Carey
Supportive care
Author’s contributions: PC conceived, wrote and revised the paper. PC read and approved the final manuscript and is the guarantor of the paper. Funding: None. Competing interests: None declared.
SCD awareness Even if progress with specific therapy has been disappointing, knowledge of the genetic basis of SCD does offer the possibility of influencing incidence. Population education is a key first step to progress and to the momentum behind the development of the political will required to implement change. There is also a role for lay population education to dispel the stigma associated with this inherited disorder, which causes a substantial additional burden of unnecessary suffering when added to the physical burdens of SCD.7
Resource allocation The different availability of effective interventions in many parts of the developed world, compared with that in resource-challenged countries, is well known. This review1 demonstrates that even within Nigeria there are stark differences in service provision: a single institution, responsible for the care of 11 000 SCD patients (46% of the 23 700 encompassed by the survey) does not have an electronic cell counter. Yet a different institution responsible for the care of 500 patients (2%) has TCD apparatus. The total 23 700 cohort only represents around 2% of the estimated 1 million SCD patients in the country and from this review we do not know anything about their care or available facilities.
International collaboration Organised implementation of specific, supportive and preventive measures can be greatly facilitated by sharing experiences.
270
Ethical approval: Not required.
References 1 Galadanci N, Wudil BJ, Balogun TM et al. Current sickle cell disease management practices in Nigeria. Int Health 2014;6:23–8. 2 Adams RJ, McKie VC, Hsu L et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 1998;339:5–11. 3 Lebensburger JD, DeBaum MR, Thompson AA. What is the evidence for using hydroxyurea for secondary stroke prevention? Hematology Am Soc Hematol Educ Program 2011;2011:440–2. 4 ClinicalTrials.gov. Sickle cell disease - Stroke Prevention in Nigeria trial (SPIN). Bethesda: U.S National Institute of Health; 2014. http://www. ClinicalTrials.gov/show/NCT01801423 [accessed 30 March 2014]. 5 Serjeant GR, Serjeant BE. Sickle Cell Disease 3rd ed. Oxford: Oxford University Press; 2001. 6 Brousse V, Makani J, Rees DC. Management of sickle cell disease in the community. BMJ 2014;348:g1765. 7 Ashiraf S. Sickle cell stigma: teach, educate, own up and speak up. Uganda: New Vision; 2013. 8 Weatherall DJ. The challenge of haemoglobinopathies in resourcepoor countries. Brit J Haematol 2011;154:736–44. 9 Carey P, Fudzulani R, Scholfield D et al. Remote and rapid pathological diagnosis in a resource challenged unit. J Clin Path 2014;67:540–3. 10 Global Sickle Cell Disease Network. Programme for global pediatric research. http://www.globalsicklecelldisease.org [accessed 11 June 2014].
Downloaded from http://inthealth.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 23, 2015
It is in the areas of supportive care provision and patient/carer/ population education where there is much ‘low hanging fruit’ in terms of making a huge difference to the worldwide burden of SCD. The well studied Jamaican cohort5 demonstrates that with appropriate antibiotic prophylaxis, good nutrition including folate supplementation, and with ready access to supportive care and surveillance for chronic problems, it is feasible for a majority of individuals with SCD to live long lives in reasonable health. Neonatal population screening and the early implementation of antibiotic prophylaxis have a huge impact on mortality. They are not expensive interventions and simply require recognition of need and political will. The process of screening itself also helps with the awareness and education of the public and of healthcare workers about SCD. Unrelated populations will have different issues from those in Nigeria. For example, in my own region in the North of England, previously there has not been a long established Afro-Caribbean population. A decade ago there were no specific services for SCD and care provision for the occasional affected individual passing through was provided on an ad-hoc basis. With the subsequent redistribution of migrants in the UK we now have a thriving cohort of adults and children with SCD. The development of the comprehensive service that we now have was greatly facilitated by the production of national guidance, development of a set of minimum standards of care provision, the operation of a supportive and constructive system of peer review nationally, and increasing awareness and provision of services in the community.6
There are plenty of examples of national and international collaborations in SCD,8 as in other areas of haematology such as leukaemia management and haematopathology diagnosis.9 An international organisation, the Global Sickle Cell Disease Network10 has formed with the goals of improving care provision and facilitating research in SCD. A next logical step for Nigeria would be to follow up this preliminary study with a further definition of the health burden: what are the main causes of SCD morbidity and mortality in the country? What are the economic, social political and medical resources needed to address those problems? How can medical care be distributed more equitably? The principles of national guideline development with consultation and collaborative ownership, and implementation with realistic standard setting and supportive peer review are well established and transferable. The most important measures with the greatest impact on mortality and morbidity are inexpensive and community-based. Countries should not use the unavailability of the ‘high-tech’ expensive interventions for the few as an excuse for failing to implement the more effective, simple and readily affordable measures for the many.
COMMENTARY
Addressing the global health burden of sickle cell disease Peter J. Carey* Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK
Received 1 April 2014; revised 13 June 2014; accepted 16 June 2014 A review of the clinical manifestations of sickle cell disease (SCD), available therapeutic interventions and a necessarily limited assessment of progress with their implementation in Nigeria (the country with the largest number of affected individuals worldwide) was recently published in this journal. Despite a disappointing dearth of targeted therapy for a condition whose molecular basis has been well understood for half a century, there is a wealth of evidence-based supportive interventions, including antibiotic and vaccination prophylaxis against early bacteraemic mortality, childhood stroke risk prevention, patient and population education and screening and community care provision that are simple and inexpensive to implement. There is a real opportunity for international collaboration to drive an improvement in healthcare provision for this condition. Keywords: Health resources, Hydroxyurea, International health problems, Sickle cell disease
Introduction In their article in International Health on the evolving medical services for sickle cell diseases (SCD) in Nigeria,1 the authors set out an excellent review of the effects of the sickling haemoglobinopathies and the available interventions. Progress with the implementation of these interventions in the country with the largest number of affected individuals worldwide was assessed by a questionnaire survey of a limited number of sickle cell centres. It is salutary to reflect, in this era of molecular diagnosis, that we have come to expect the regular and numerous pharmacological developments of effective targeted therapies for many haematological malignancies. Yet, 50 years since the molecular coding and structural abnormalities in SCD were fully described, there is a dearth of specific treatments for these conditions. The most applicable interventions are indirect and supportive, though potential strategies for prevention have been informed by molecular understanding.
Specific therapy As far as specific therapies are concerned, there is haemopoietic stem cell transplantation, red cell transfusion therapy and hydroxyurea (HU) (hydroxycarbamide). Haemopoietic stem cell transplantation remains the only potentially curative option. Despite the huge complexity and expense that is always going to restrict its availability, it is still a rather blunt instrument fraught with morbidity and mortality. Chronic transfusion therapy, even when available, is complicated by problems related to iron overload, chelation, alloimmunisation and venous access issues. In countries like Nigeria where transfusion services rely heavily
on family donors, the difficulty in SCD is that blood from individuals with sickle cell trait (or of course with the disease itself) is not suitable, which precludes donation by the majority of siblings and parents. The accidental discovery of the beneficial effects of HU on the incidence of complications in SCD is important in terms of its potential wider applicability, with the availability of regular blood counts and patient and healthcare provider education, the only barriers to safer implementation on a wider scale. Childhood stroke has been a major disease burden in SCD patients surviving infancy. A potential childhood intervention in SCD follows the demonstration of the preventive effects of chronic transfusion for stroke risk, and the ability to identify at-risk individuals by ultrasonic transcranial Doppler (TCD) screening.2 The implementation of TCD screening programmes has been a major focus in western countries. There has been little point in doing so in countries where the required transfusion therapy is not then going to be available for the individuals identified. The work on stroke risk prevention with transfusion was undertaken before the beneficial effects of HU in SCD were recognised. There is an urgent need for evidence on the potential effect of HU in this area and whether or not it might be comparable with that of transfusion. There are anectodal suggestions that HU may be at least partially effective,3 and if this were demonstrable the prospects of achievable access to an effective intervention are much more realistic. The proposed Stroke Prevention in Nigeria (SPIN) trial,4 though not directly comparing the two interventions, is ideally placed to address the question of whether there is an important HU effect and the international sickle community will await its outcome with great interest. Wider implementation of HU therapy would be challenging, but more readily achievable than chronic transfusion therapy.
# The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: [email protected].
269
Downloaded from http://inthealth.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 23, 2015
*Corresponding author: Tel: +44 191 282 4743; E-mail: [email protected]
P. J. Carey
Supportive care
Author’s contributions: PC conceived, wrote and revised the paper. PC read and approved the final manuscript and is the guarantor of the paper. Funding: None. Competing interests: None declared.
SCD awareness Even if progress with specific therapy has been disappointing, knowledge of the genetic basis of SCD does offer the possibility of influencing incidence. Population education is a key first step to progress and to the momentum behind the development of the political will required to implement change. There is also a role for lay population education to dispel the stigma associated with this inherited disorder, which causes a substantial additional burden of unnecessary suffering when added to the physical burdens of SCD.7
Resource allocation The different availability of effective interventions in many parts of the developed world, compared with that in resource-challenged countries, is well known. This review1 demonstrates that even within Nigeria there are stark differences in service provision: a single institution, responsible for the care of 11 000 SCD patients (46% of the 23 700 encompassed by the survey) does not have an electronic cell counter. Yet a different institution responsible for the care of 500 patients (2%) has TCD apparatus. The total 23 700 cohort only represents around 2% of the estimated 1 million SCD patients in the country and from this review we do not know anything about their care or available facilities.
International collaboration Organised implementation of specific, supportive and preventive measures can be greatly facilitated by sharing experiences.
270
Ethical approval: Not required.
References 1 Galadanci N, Wudil BJ, Balogun TM et al. Current sickle cell disease management practices in Nigeria. Int Health 2014;6:23–8. 2 Adams RJ, McKie VC, Hsu L et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 1998;339:5–11. 3 Lebensburger JD, DeBaum MR, Thompson AA. What is the evidence for using hydroxyurea for secondary stroke prevention? Hematology Am Soc Hematol Educ Program 2011;2011:440–2. 4 ClinicalTrials.gov. Sickle cell disease - Stroke Prevention in Nigeria trial (SPIN). Bethesda: U.S National Institute of Health; 2014. http://www. ClinicalTrials.gov/show/NCT01801423 [accessed 30 March 2014]. 5 Serjeant GR, Serjeant BE. Sickle Cell Disease 3rd ed. Oxford: Oxford University Press; 2001. 6 Brousse V, Makani J, Rees DC. Management of sickle cell disease in the community. BMJ 2014;348:g1765. 7 Ashiraf S. Sickle cell stigma: teach, educate, own up and speak up. Uganda: New Vision; 2013. 8 Weatherall DJ. The challenge of haemoglobinopathies in resourcepoor countries. Brit J Haematol 2011;154:736–44. 9 Carey P, Fudzulani R, Scholfield D et al. Remote and rapid pathological diagnosis in a resource challenged unit. J Clin Path 2014;67:540–3. 10 Global Sickle Cell Disease Network. Programme for global pediatric research. http://www.globalsicklecelldisease.org [accessed 11 June 2014].
Downloaded from http://inthealth.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 23, 2015
It is in the areas of supportive care provision and patient/carer/ population education where there is much ‘low hanging fruit’ in terms of making a huge difference to the worldwide burden of SCD. The well studied Jamaican cohort5 demonstrates that with appropriate antibiotic prophylaxis, good nutrition including folate supplementation, and with ready access to supportive care and surveillance for chronic problems, it is feasible for a majority of individuals with SCD to live long lives in reasonable health. Neonatal population screening and the early implementation of antibiotic prophylaxis have a huge impact on mortality. They are not expensive interventions and simply require recognition of need and political will. The process of screening itself also helps with the awareness and education of the public and of healthcare workers about SCD. Unrelated populations will have different issues from those in Nigeria. For example, in my own region in the North of England, previously there has not been a long established Afro-Caribbean population. A decade ago there were no specific services for SCD and care provision for the occasional affected individual passing through was provided on an ad-hoc basis. With the subsequent redistribution of migrants in the UK we now have a thriving cohort of adults and children with SCD. The development of the comprehensive service that we now have was greatly facilitated by the production of national guidance, development of a set of minimum standards of care provision, the operation of a supportive and constructive system of peer review nationally, and increasing awareness and provision of services in the community.6
There are plenty of examples of national and international collaborations in SCD,8 as in other areas of haematology such as leukaemia management and haematopathology diagnosis.9 An international organisation, the Global Sickle Cell Disease Network10 has formed with the goals of improving care provision and facilitating research in SCD. A next logical step for Nigeria would be to follow up this preliminary study with a further definition of the health burden: what are the main causes of SCD morbidity and mortality in the country? What are the economic, social political and medical resources needed to address those problems? How can medical care be distributed more equitably? The principles of national guideline development with consultation and collaborative ownership, and implementation with realistic standard setting and supportive peer review are well established and transferable. The most important measures with the greatest impact on mortality and morbidity are inexpensive and community-based. Countries should not use the unavailability of the ‘high-tech’ expensive interventions for the few as an excuse for failing to implement the more effective, simple and readily affordable measures for the many.
