REVIEW URRENT C OPINION
Sickle cell disease in sub-Saharan Africa: stakes and strategies for control of the disease Dapa A. Diallo and Aldiouma Guindo
Purpose of review In the late 1990s publications on cohorts of sickle cell disease (SCD) patients, followed since birth, showed that the life expectancy of SCD patients in developed countries could approach that of those without SCD, when managed appropriately. Between 2005 and 2008, SCD was declared as a public health priority issue worldwide. In 2006, the WHO recommended that African states should include the fight against SCD in their health policies. Nevertheless, there are, as of yet, no data on effective strategies to implement SCD control in these countries. This review discusses the stakes and proposes strategies for SCD management and research in sub-Saharan Africa. Recent findings This work is a review of the recent literature on the burden of SCD in sub-Saharan Africa; on approaches that resulted in improved survival and comfort for SCD patients in developed countries; and, in contrast, on the inadequacies of most issues relating to the fight against SCD in Africa. Summary Multiple constraints require an organization based on a network of health professionals working in sickle cell referral centers with specific missions of research, communication, teaching, establishment of guidelines for diagnosis, treatment, and prevention, and the centers of competence that will focus primarily on the screening, diagnosis, and management of SCD patients favoring equity in access to care. Keywords control, sickle cell disease, stakes, strategies, sub-Saharan Africa
INTRODUCTION Sickle cell disease (SCD) is the most common hemoglobin defect worldwide, with a high incidence in sub-Saharan Africa. In the late 1990s publications from large cohort studies of SCD patients (followed from birth) in developed countries showed that the life expectancy of such patients could be improved, even without the use of sophisticated and expensive means [1]. Subsequently, between 2005 and 2008, SCD was recognized as a public health priority issue in the world, first by the African Union and then by the United Nations Educational, Scientific and Cultural Organization, the WHO, and the United Nations. However, in Africa, where the disease is common, little progress has been achieved even though guidelines were provided to the countries by the decision-making bodies in the fight against SCD. To our knowledge, data are yet to be published concerning the stakes and strategies for a holistic management of SCD in sub-Saharan countries. www.co-hematology.com
BURDEN OF SICKLE CELL DISEASE IN AFRICA AND LACK OF OVERALL MANAGEMENT OF VITAL COMPLICATIONS SCD was described in Africa under several names long before its clinical description by Herrick in 1910 [2–4]. According to demographic forecasts, the number of sickle cell births will increase from 304 800 in 2010 to 404 200 in 2050 worldwide. Of these births, more than 85% will occur in sub-Saharan Africa [5 ], where SCD accounts for approximately 1% of live births. Despite this high incidence, Africa remains a continent in which SCD is still a neglected disease [6,7]. According to the WHO, mortality in Africa due to SCD varies &&
Centre de Recherche et de Lutte contre la Dre´panocytose, Bamako, Mali Correspondence to Professor Dapa A. Diallo, Centre de Recherche et de Lutte contre la Dre´panocytose, 03 BP: 186 BKO 03, Bamako, Mali. Tel: +(223) 20 22 3898; e-mail: [email protected] Curr Opin Hematol 2014, 21:210–214 DOI:10.1097/MOH.0000000000000038 Volume 21 Number 3 May 2014
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Sickle cell disease control in sub-Saharan Africa Diallo and Guindo
KEY POINTS The two major stakes of the fight against SCD in subSaharan Africa are reducing SCD births and improving SCD patients’ survival and quality of life. Reducing the number of SCD births, the most effective way to control the disease, implies the introduction of teaching on SCD early in school educational programs and screening followed by genetic counseling for teenagers. The objective to improve SCD patients’ survival and quality of life will be achieved by the creation of SCRCs with sufficient staff and means, which have capabilities to design efficacious programs for research, training, information, and early screening and to organize specific care within centers and units of competence. Health policies favoring equity in access to care and nonpayment of medical expenses before the care are needed for the success of these strategies, and imply commitment of states as well an international decisionmaking.
between 5 and 19% of overall mortality in the population of children under 5 years of age [8]. This means that if effective strategies of disease care and prevention are not implemented, infant mortality related to SCD in Africa could reach more than 150 000 deaths every 5 years. This high mortality reflects the lack of early diagnosis, appropriate prevention, and management of lifethreatening complications. In many cases, death occurs in undiagnosed children, during early infancy, and is erroneously attributed to malaria or infections, which are in fact secondary events [9]. Access to tools allowing timely screening for these complications [10–12] and access to therapeutics that can improve the prognosis of SCD are limited [13,14 ,15 ]. Hydroxycarbamide, which should be manufactured in Africa and provided at a reasonable price, is too expensive for most patients. Medical education about management of pain is insufficient, and the amount of morphine prescribed for vaso-occlusive crises is far from meeting patient needs [16 ]. Blood transfusions meet less than 50% of demands, and transfusion safety is often questionable [17]. Bacterial infections remain major purveyors of death without any antibiotic consensus established by the bias of randomized controlled trials. Moreover, vaccinations against infections, which are not included in the WHO program, such as pneumococcus, meningococcus, or salmonella, are far beyond the financial access of most families [18,19]. A consensus should be reached for the prevention of malaria, &
&&
&
which is a major cause of death in SCD children in sub-Saharan Africa [20–22], but also specifically in adults, through international African therapeutic trials. A regular follow-up should screen for complications such as osteonecrosis or osteomyelitis at an early phase. The management of pregnancies in SCD-affected women, which carry a high risk of maternal and fetal morbidity and mortality, should be a major concern and lead to the close collaboration of obstetricians and hematologists. Ultimately, some complications of SCD will become of further concern in Africa [23 ]. &&
ISSUES IN THE FIGHT AGAINST SICKLE CELL DISEASE IN SUB-SAHARAN AFRICA Africa has to face two major challenges: improving life expectancy and quality of life in SCD patients, while reducing the number of sickle cell births. Importantly, the first priority in the fight against SCD in sub-Saharan Africa is to ensure equitable access to specific care for patients, regardless of their socioeconomic status. It should be emphasized that the majority of people affected by SCD are those with a limited income as reported by the Human Development Index [24]. In most African countries, only rich patients can have access to basic treatments such as prophylactic oral penicillin. Fighting against such inequality claims for the widespread need of effective care. Specifically, access to emergency care must not be dependent upon prior payment of fees. A major demanding issue is the training of a critical mass of healthcare workers to ensure the correct management of SCD patients in either a steady state or those suffering from acute complications. The third stake is to educate and effectively inform the population in order to reach a positive change in behavior leading to a reduction in unions that bear a risk of birth of SCD-affected infants. The fourth issue is research aiming to define the most appropriate approaches. Referral centers from several countries have to collaborate and reach a consensus on major concerns in management.
STRATEGIES FOR THE HOLISTIC CARE OF SICKLE CELL DISEASE IN AFRICA In its resolution of the World Health Assembly 59.20, 27 May 2006, the WHO recommended that African states integrate the fight against SCD in their national health policies. To be effective, these policies have to include approaches to improve care, early diagnosis, and disease prevention as well as the training for capacities to screen, diagnose, and provide an efficacious management of the disease complications.
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Organization of sickle cell disease-specific care in Africa Specific care must be based on a system of networks of centers and units of competence coordinated by sickle cell referral centers (SCRCs), whose status depends on the resources and health policies of each country. Three questions must be raised in defining the missions of these SCRCs: at what level of the health pyramid should they be built by what means and with which policy of access to care? Answers to these questions depend on the weight of the multiple constraints to be considered, which arise from factors including disease, geography, health organization, and representations that patients and families have of the disease and of the capacity of health facilities. Constraints related to the disease In Africa, SCD is still primarily a disease of emergency; management of acute complications implies the possibility of access to a trained team for patients in a timely manner. Meeting this constraint involves the multiplication of health workers who have been trained in a referral center with subsequent tests on their level of knowledge and reactivity, on their ability to diagnose complications at their onset, and their skill at convincing patients of the vital necessity of a regular follow-up, even when in a steady state. Constraints of geography Sub-Saharan African states are large states often characterized by impracticable roads and limited transport, which reduce the ability to manage SCD emergencies, and can lead to urban migration of families with one or several affected children whenever possible. Constraints related to the organization of health structures Since the Bamako Initiative in 1987 [25], the organization of health systems in sub-Saharan African countries follows a scheme of pyramidal reference. At the base of the pyramid are the structures of community health, managed by community associations, which are easily accessible, but have limited resources; they ensure referrals to the district hospitals, which often lack resources for specific support. Public hospital establishments are the last baseline, with more resources in terms of trained care providers and equipment. These structures are mostly located in capitals, and access is difficult for the majority of patients because of distance, and the cost of services provided. The policy of all structures is cost recovery with a fee payment before access to specialized consultations, 212
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a situation which in many cases can lead to death while family members are trying to resolve the financial issue in a context of extreme poverty [24]. Constraints related to patient SCD is unfortunately considered in several subSaharan African countries as a disease of the sorcerer, incompatible with a working long-term life. Such depictions induce attitudes that favor fatalism or the use of traditional treatments and delay efficacious therapies. Taking into account these constraints, SCD-SCRCs in Africa should fulfill a number of missions, such as design, organization, coordination and monitoring/evaluation, training, education, and research. The design mission consists of adapting and developing the most comprehensive regimens to a given African context, including relevant training programs, and promoting effective tools for communication. The organizational mission focuses on diagnosis and management procedures. The mission of coordinating and monitoring/evaluation will take into account information derived from the follow-up of SCD patient cohorts. The mission of training and specifically of promoting awareness and proper management of emergencies has to concern staff of all levels on the health pyramid, even in remote villages, through classical classroom training as well as e-learning. The research mission should focus initially on clinical research across well monitored cohorts of SCD patients. Anthropological and, secondly, fundamental research will help in understanding the issues arising from the clinical research data. Finally, to avoid diverting the SCRCs from these core tasks, their involvement in care should be considered mostly for specialized and programmable care (e.g., new therapies and hematopoietic stem cell transplantation) or costly explorations, which are not accessible to all levels of care (e.g., detection of children at risk for neurological complications by transcranial Doppler, erythrapheresis, hip surgery. . .). The experience of the ‘Centre de Recherche et de Lutte contre la Dre´panocytose de Bamako’, Mali shows that a regular follow-up of SCD-affected individuals can be achieved on a large scale. However, the continuous increase in patient cohort (500–800 patients/year) suggests a necessary increase in the number of staff in order to face the demand while preserving the quality of management, research, and teaching.
Centers and units of competence for management of sickle cell disease in sub-Saharan Africa SCD cannot be the matter of a single highly specialized center. Building centers and units of competence Volume 21 Number 3 May 2014
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Sickle cell disease control in sub-Saharan Africa Diallo and Guindo
is vital. These structures, whose missions should focus primarily on diagnosis and management, should be in the proximity of the patients. They are the stepping stones necessary to promote access to timely care for a great number of SCD patients, at an affordable cost. Monitoring of patients should follow the standards issued by the SCRC. Centers and units of competence must work to ultimately build a network of health professionals communicating effectively with each other and with those of the SCRC. The current development of information and communication technology favors communications. The goal of equal access to healthcare can only be achieved if health policies guarantee effective care for all patients in a context of poverty. In failing to consider free healthcare, which seems unrealistic, the availability of emergency kits for SCD acute complications, such as free specific vaccines, in all structures of care regardless of patients’ socioeconomic status, are the first steps that could reduce mortality and improve quality of life.
Challenge of early diagnosis and prevention of disease Early diagnosis of SCD in sub-Saharan Africa is a mandatory preventive strategy for complications in SCD-affected newborns. The question is: when and how it should be conducted? Screening should be included in the minimum package of activities for all structures that aid in the delivery of newborns and requires prior studies to define the more efficient approaches considering the high cost of diagnosis. The first studies concerning early diagnosis are pilot studies [26–28], which highlight two important findings: screening at birth can be burdened by difficulties in reaching all SCD-screened children [29], and strategies depend on phenotype distributions (Diallo, oral communication). The best approach would be a combination of screening at birth and subsequently during the course of the extended current vaccination programs. The effectiveness of this approach will depend highly on a rigorous network that allows information on SCD-affected infants and their families to be readily available and accessed with minimal delay. The geographical positioning systems can be of great help. Prevention of SCD births is indisputably the most effective way of managing the long-term issue of SCD in subSaharan Africa. Newborn screening that detects SCD-affected as well as heterozygous newborns must lead to genetic counseling whenever both parents are heterozygous. However, such
information is generally provided a long time after the decision to establish a matrimonial home has been made. Effectiveness in the prevention of sickle cell births will result from the combination of two strategies: an introduction to SCD and teaching early on in school educational programs and screening followed by genetic counseling for teenagers, an age in which most wedding plans are initiated.
Research and training Studies following large cohorts of SCD patients from birth are still lacking in Africa, hampering information on key issues regarding the nature of this disease, predominantly, the main causes of SCD-related deaths, the spectrum of complications and age of onset, the psychological impact on SCD patients and their families, and the insertion issues in working life. The goal of improving survival and patient quality of life through equitable access to specific care raises questions that must be considered: what are the identifiable risk factors for occurrence of complications; how to improve blood transfusion accessibility and security; and how to promote access to protocols, including morphine and hydroxycarbamide at an affordable cost? The lack of comprehensive data on the causes of worsening anemia in SCD in sub-Saharan Africa dictates the need for further research focusing particularly on the impact of malaria and of the erythrovirus B19 in mortality due to severe anemia [30].
CONCLUSION Despite multiple constraints in sub-Saharan Africa, including building capacity for the diagnosis and management of SCD emergencies and creating structures near communities developing networks with a SCRC, it is possible that strategies based on a goal of holistic care for SCD can improve the life expectancy of patients and reduce SCD births across the continent. The success of such strategies is dependent upon the commitment of states and policies favoring innovative equal access to healthcare, a close collaboration between SCRCs of different countries and also an international commitment. Acknowledgements We acknowledge Narla Mohandas and Gil Tchernia for their advice and scientific support. Conflicts of interest There are no conflicts of interest.
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REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Serjeant GR, Serjeant BE. Management of sickle cell disease; lessons from the Jamaican Cohort Study. Blood 1993; 7:137–145. 2. Nzewi E. Recurrent reincarnation or sickle cell disease? Soc Sci Med 2001; 52:1403–1416. 3. Onwubalili JK. Sickle-cell anaemia: an explanation for the ancient myth of reincarnation in Nigeria. Lancet 1983; 2:503–505. 4. Tchernia G. The long story of the sickle cell disease. Rev Prat 2004; 54:1618–1621. 5. Piel FB, Hay SI, Gupta S, et al. Global burden of sickel cell anaemia in children && under five, 2010–2050: modelling based on demographics, excess mortality, and interventions. PloS Med 2013; 10:e1001484. This work built on an original analytical methodology invites to build appropriate strategies notably newborn screening and development of capacity to reduce sickle cell anemia mortality in Africa. 6. Weatherall D. The inherited disorders of haemoglobin: an increasing neglected health burden. Blood 2010; 115:4331–4336. 7. Ware RE. Is sickle cell anemia a neglected tropical disease? PloS Negl Trop Dis 2013; 7:e2120. 8. WHO World Health Organization. Sickle-cell anaemia. Report A59/9. WHO: Geneva, Switzerland; 2006. 9. Diallo D, Baby M, Boire´ A, Diallo YL. Management of vaso-occlusive crisis in sickle cell anemia patients by health workers in Mali. Med Trop 2008; 68:502–506. 10. Bernaudin F, Verlhac S, Arnaud C, et al. Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort. Blood 2011; 117:1130– 1140. 11. Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 1998; 91: 288–294. 12. Makenzie JD, Hernandez A, Pena A, et al. Magnetic resonance imaging in child with sickle cell disease: detecting alterations in the apparent diffusion coefficient in hips with avascular necrosis. Pediatr Radiol 2012; 42:706– 7013. 13. Lucarelli G, Isgro` A, Sodani P, Gaziev J. Hematopoietic stem cell transplantation in thalassemia and sickle cell anemia. Perspect Med 2012; 2:a011825. 14. Wang WC, Oyeku SO, Luo Z, et al. Hydroxyurea is associated with lower & costs of care of young children with sickle cell anemia. Pediatrics 2013; 132:677–683. This study underlines the necessity for sub-Saharan Africa countries to build means to access to hydroxyurea for sickle cell anemia patients, as it improves their quality of life and reduces the cost of care.
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15. Jain D, Apte M, Colah R, et al. Efficacy of fixed low dose hydroxyurea in Indian children with sickle cell anemia: a single centre experience. Indian Pediatr 2013; 50:929–933. Results of this work invite to conduct multicenter studies in all countries with lower income and facilities for the biological management of patients. 16. Madadi P, Enato EF, Fulga S, et al. Patterns of paediatric analgesic use & in Africa: a systematic review. Arch Dis Child 2012; 97:1086–1091. This study analyzed 35 observational studies on 1772 suffering children in 12 African countries and shows that morphine was used in 0.2%, underlining the great failure of the treatment of pain in children and need for urgent strategies in sub-Saharan Africa. 17. Bloch EM, Vermeulen M, Murphy E. Blood transfusion safety in Africa: a literature review of infectious disease and organization challenges. Transfus Med Rev 2012; 26:164–180. 18. Narang S, Fernandez ID, Chin N, et al. Becteremia in children with sickle hemoglobinopathies. J Pedaitr Hematol Oncol 2012; 34:13–16. 19. Marti-carvajal AJ, Agreda-Pe´rez LH. Antibiotics for treating osteomylitis in people with sickle cell disease. Cochrane Database Syst Rev 2012; 12:CD007175. 20. Makani J, Komba AN, Cox SE, et al. Malaria in patients with sickle cell anemia: burden, risk factors, and outcome at the outpatients clinic and during hospitalization. Blood 2010; 115:215–220. 21. Komba AN, Makani J, Sadarangani M, et al. Malaria as a cause of morbidity and mortality in chlidren with homozygous sickle cell disease on the coast of Kenya. Clin Infect Dis 2009; 49:216–222. 22. Aidoo M, Terlouw DJ, Kolczak MS, et al. Protective effects of sickle cell gene against malaria morbidity and mortality. Lancet 2002; 259:1311–1312. 23. Diallo DA, Thiam MM, Ranque B, Jouven X, the DACDRE Study group && [abstract]. Glome´rulopathie dre´panocytaire: re´sultats de l’e´tude CADRE. VIIe`me congre`s de la Socie´te´ Africaine Francophone d’He´matologie (SAFHEMA), Antanarivo, Madagascar. 13–15 Novembre 2013. This is the first collaborative work, involving research teams from France and five countries in West Africa, which focused on 2931 children with SCD during the steady phase to determine the age of onset of glomeropathy and its frequency. It highlights the necessity to rapidly include the detection of this complication in the survey of sickle cell anemia patients in sub-Saharan Africa. 24. United Nations Development Programme. Human Development Report 2013. UNDP; 2013. 25. Fassin. Gentilini M. The Bamako initiative [letter]. Lancet 1989; 1:162–163. 26. Ohene-frempong K, Oduro J, Tetteh H, Nkruma F. Screening newborn for sickle cell disease in Ghana. Pediatrics 2008; 121:S120–121. 27. Rahimy MC, Gangbo A, Ahouigan G, Alihonou E. Newborn screening for sickle cell disease in Republic of Benin. J Clin Pathol 2009; 62:46–48. 28. Tshilolo L, Assi LM, Lukusa D, et al. Neonatal screening for sickle cell anaemia in the Democratic Republic of the Congo: experience from a pioneer project on 31204 newborns. J Clin Pathol 2009; 62:35–38. 29. Diallo D. Sickle cell disease in Africa: current situation and strategies for improving the quality and duration of survival. Bull Acad Natl Me´d 2008; 192:1361–1373. 30. Diallo DA, Guindo A, Dorie A, et al. Human parvovirus B19 infection in sickle cell anemia patient in Mali: a case-control study. Arch Pediatr 2011; 18:962– 965. &&
Volume 21 Number 3 May 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Sickle cell disease in sub-Saharan Africa: stakes and strategies for control of the disease Dapa A. Diallo and Aldiouma Guindo
Purpose of review In the late 1990s publications on cohorts of sickle cell disease (SCD) patients, followed since birth, showed that the life expectancy of SCD patients in developed countries could approach that of those without SCD, when managed appropriately. Between 2005 and 2008, SCD was declared as a public health priority issue worldwide. In 2006, the WHO recommended that African states should include the fight against SCD in their health policies. Nevertheless, there are, as of yet, no data on effective strategies to implement SCD control in these countries. This review discusses the stakes and proposes strategies for SCD management and research in sub-Saharan Africa. Recent findings This work is a review of the recent literature on the burden of SCD in sub-Saharan Africa; on approaches that resulted in improved survival and comfort for SCD patients in developed countries; and, in contrast, on the inadequacies of most issues relating to the fight against SCD in Africa. Summary Multiple constraints require an organization based on a network of health professionals working in sickle cell referral centers with specific missions of research, communication, teaching, establishment of guidelines for diagnosis, treatment, and prevention, and the centers of competence that will focus primarily on the screening, diagnosis, and management of SCD patients favoring equity in access to care. Keywords control, sickle cell disease, stakes, strategies, sub-Saharan Africa
INTRODUCTION Sickle cell disease (SCD) is the most common hemoglobin defect worldwide, with a high incidence in sub-Saharan Africa. In the late 1990s publications from large cohort studies of SCD patients (followed from birth) in developed countries showed that the life expectancy of such patients could be improved, even without the use of sophisticated and expensive means [1]. Subsequently, between 2005 and 2008, SCD was recognized as a public health priority issue in the world, first by the African Union and then by the United Nations Educational, Scientific and Cultural Organization, the WHO, and the United Nations. However, in Africa, where the disease is common, little progress has been achieved even though guidelines were provided to the countries by the decision-making bodies in the fight against SCD. To our knowledge, data are yet to be published concerning the stakes and strategies for a holistic management of SCD in sub-Saharan countries. www.co-hematology.com
BURDEN OF SICKLE CELL DISEASE IN AFRICA AND LACK OF OVERALL MANAGEMENT OF VITAL COMPLICATIONS SCD was described in Africa under several names long before its clinical description by Herrick in 1910 [2–4]. According to demographic forecasts, the number of sickle cell births will increase from 304 800 in 2010 to 404 200 in 2050 worldwide. Of these births, more than 85% will occur in sub-Saharan Africa [5 ], where SCD accounts for approximately 1% of live births. Despite this high incidence, Africa remains a continent in which SCD is still a neglected disease [6,7]. According to the WHO, mortality in Africa due to SCD varies &&
Centre de Recherche et de Lutte contre la Dre´panocytose, Bamako, Mali Correspondence to Professor Dapa A. Diallo, Centre de Recherche et de Lutte contre la Dre´panocytose, 03 BP: 186 BKO 03, Bamako, Mali. Tel: +(223) 20 22 3898; e-mail: [email protected] Curr Opin Hematol 2014, 21:210–214 DOI:10.1097/MOH.0000000000000038 Volume 21 Number 3 May 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Sickle cell disease control in sub-Saharan Africa Diallo and Guindo
KEY POINTS The two major stakes of the fight against SCD in subSaharan Africa are reducing SCD births and improving SCD patients’ survival and quality of life. Reducing the number of SCD births, the most effective way to control the disease, implies the introduction of teaching on SCD early in school educational programs and screening followed by genetic counseling for teenagers. The objective to improve SCD patients’ survival and quality of life will be achieved by the creation of SCRCs with sufficient staff and means, which have capabilities to design efficacious programs for research, training, information, and early screening and to organize specific care within centers and units of competence. Health policies favoring equity in access to care and nonpayment of medical expenses before the care are needed for the success of these strategies, and imply commitment of states as well an international decisionmaking.
between 5 and 19% of overall mortality in the population of children under 5 years of age [8]. This means that if effective strategies of disease care and prevention are not implemented, infant mortality related to SCD in Africa could reach more than 150 000 deaths every 5 years. This high mortality reflects the lack of early diagnosis, appropriate prevention, and management of lifethreatening complications. In many cases, death occurs in undiagnosed children, during early infancy, and is erroneously attributed to malaria or infections, which are in fact secondary events [9]. Access to tools allowing timely screening for these complications [10–12] and access to therapeutics that can improve the prognosis of SCD are limited [13,14 ,15 ]. Hydroxycarbamide, which should be manufactured in Africa and provided at a reasonable price, is too expensive for most patients. Medical education about management of pain is insufficient, and the amount of morphine prescribed for vaso-occlusive crises is far from meeting patient needs [16 ]. Blood transfusions meet less than 50% of demands, and transfusion safety is often questionable [17]. Bacterial infections remain major purveyors of death without any antibiotic consensus established by the bias of randomized controlled trials. Moreover, vaccinations against infections, which are not included in the WHO program, such as pneumococcus, meningococcus, or salmonella, are far beyond the financial access of most families [18,19]. A consensus should be reached for the prevention of malaria, &
&&
&
which is a major cause of death in SCD children in sub-Saharan Africa [20–22], but also specifically in adults, through international African therapeutic trials. A regular follow-up should screen for complications such as osteonecrosis or osteomyelitis at an early phase. The management of pregnancies in SCD-affected women, which carry a high risk of maternal and fetal morbidity and mortality, should be a major concern and lead to the close collaboration of obstetricians and hematologists. Ultimately, some complications of SCD will become of further concern in Africa [23 ]. &&
ISSUES IN THE FIGHT AGAINST SICKLE CELL DISEASE IN SUB-SAHARAN AFRICA Africa has to face two major challenges: improving life expectancy and quality of life in SCD patients, while reducing the number of sickle cell births. Importantly, the first priority in the fight against SCD in sub-Saharan Africa is to ensure equitable access to specific care for patients, regardless of their socioeconomic status. It should be emphasized that the majority of people affected by SCD are those with a limited income as reported by the Human Development Index [24]. In most African countries, only rich patients can have access to basic treatments such as prophylactic oral penicillin. Fighting against such inequality claims for the widespread need of effective care. Specifically, access to emergency care must not be dependent upon prior payment of fees. A major demanding issue is the training of a critical mass of healthcare workers to ensure the correct management of SCD patients in either a steady state or those suffering from acute complications. The third stake is to educate and effectively inform the population in order to reach a positive change in behavior leading to a reduction in unions that bear a risk of birth of SCD-affected infants. The fourth issue is research aiming to define the most appropriate approaches. Referral centers from several countries have to collaborate and reach a consensus on major concerns in management.
STRATEGIES FOR THE HOLISTIC CARE OF SICKLE CELL DISEASE IN AFRICA In its resolution of the World Health Assembly 59.20, 27 May 2006, the WHO recommended that African states integrate the fight against SCD in their national health policies. To be effective, these policies have to include approaches to improve care, early diagnosis, and disease prevention as well as the training for capacities to screen, diagnose, and provide an efficacious management of the disease complications.
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Erythroid system and its diseases
Organization of sickle cell disease-specific care in Africa Specific care must be based on a system of networks of centers and units of competence coordinated by sickle cell referral centers (SCRCs), whose status depends on the resources and health policies of each country. Three questions must be raised in defining the missions of these SCRCs: at what level of the health pyramid should they be built by what means and with which policy of access to care? Answers to these questions depend on the weight of the multiple constraints to be considered, which arise from factors including disease, geography, health organization, and representations that patients and families have of the disease and of the capacity of health facilities. Constraints related to the disease In Africa, SCD is still primarily a disease of emergency; management of acute complications implies the possibility of access to a trained team for patients in a timely manner. Meeting this constraint involves the multiplication of health workers who have been trained in a referral center with subsequent tests on their level of knowledge and reactivity, on their ability to diagnose complications at their onset, and their skill at convincing patients of the vital necessity of a regular follow-up, even when in a steady state. Constraints of geography Sub-Saharan African states are large states often characterized by impracticable roads and limited transport, which reduce the ability to manage SCD emergencies, and can lead to urban migration of families with one or several affected children whenever possible. Constraints related to the organization of health structures Since the Bamako Initiative in 1987 [25], the organization of health systems in sub-Saharan African countries follows a scheme of pyramidal reference. At the base of the pyramid are the structures of community health, managed by community associations, which are easily accessible, but have limited resources; they ensure referrals to the district hospitals, which often lack resources for specific support. Public hospital establishments are the last baseline, with more resources in terms of trained care providers and equipment. These structures are mostly located in capitals, and access is difficult for the majority of patients because of distance, and the cost of services provided. The policy of all structures is cost recovery with a fee payment before access to specialized consultations, 212
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a situation which in many cases can lead to death while family members are trying to resolve the financial issue in a context of extreme poverty [24]. Constraints related to patient SCD is unfortunately considered in several subSaharan African countries as a disease of the sorcerer, incompatible with a working long-term life. Such depictions induce attitudes that favor fatalism or the use of traditional treatments and delay efficacious therapies. Taking into account these constraints, SCD-SCRCs in Africa should fulfill a number of missions, such as design, organization, coordination and monitoring/evaluation, training, education, and research. The design mission consists of adapting and developing the most comprehensive regimens to a given African context, including relevant training programs, and promoting effective tools for communication. The organizational mission focuses on diagnosis and management procedures. The mission of coordinating and monitoring/evaluation will take into account information derived from the follow-up of SCD patient cohorts. The mission of training and specifically of promoting awareness and proper management of emergencies has to concern staff of all levels on the health pyramid, even in remote villages, through classical classroom training as well as e-learning. The research mission should focus initially on clinical research across well monitored cohorts of SCD patients. Anthropological and, secondly, fundamental research will help in understanding the issues arising from the clinical research data. Finally, to avoid diverting the SCRCs from these core tasks, their involvement in care should be considered mostly for specialized and programmable care (e.g., new therapies and hematopoietic stem cell transplantation) or costly explorations, which are not accessible to all levels of care (e.g., detection of children at risk for neurological complications by transcranial Doppler, erythrapheresis, hip surgery. . .). The experience of the ‘Centre de Recherche et de Lutte contre la Dre´panocytose de Bamako’, Mali shows that a regular follow-up of SCD-affected individuals can be achieved on a large scale. However, the continuous increase in patient cohort (500–800 patients/year) suggests a necessary increase in the number of staff in order to face the demand while preserving the quality of management, research, and teaching.
Centers and units of competence for management of sickle cell disease in sub-Saharan Africa SCD cannot be the matter of a single highly specialized center. Building centers and units of competence Volume 21 Number 3 May 2014
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Sickle cell disease control in sub-Saharan Africa Diallo and Guindo
is vital. These structures, whose missions should focus primarily on diagnosis and management, should be in the proximity of the patients. They are the stepping stones necessary to promote access to timely care for a great number of SCD patients, at an affordable cost. Monitoring of patients should follow the standards issued by the SCRC. Centers and units of competence must work to ultimately build a network of health professionals communicating effectively with each other and with those of the SCRC. The current development of information and communication technology favors communications. The goal of equal access to healthcare can only be achieved if health policies guarantee effective care for all patients in a context of poverty. In failing to consider free healthcare, which seems unrealistic, the availability of emergency kits for SCD acute complications, such as free specific vaccines, in all structures of care regardless of patients’ socioeconomic status, are the first steps that could reduce mortality and improve quality of life.
Challenge of early diagnosis and prevention of disease Early diagnosis of SCD in sub-Saharan Africa is a mandatory preventive strategy for complications in SCD-affected newborns. The question is: when and how it should be conducted? Screening should be included in the minimum package of activities for all structures that aid in the delivery of newborns and requires prior studies to define the more efficient approaches considering the high cost of diagnosis. The first studies concerning early diagnosis are pilot studies [26–28], which highlight two important findings: screening at birth can be burdened by difficulties in reaching all SCD-screened children [29], and strategies depend on phenotype distributions (Diallo, oral communication). The best approach would be a combination of screening at birth and subsequently during the course of the extended current vaccination programs. The effectiveness of this approach will depend highly on a rigorous network that allows information on SCD-affected infants and their families to be readily available and accessed with minimal delay. The geographical positioning systems can be of great help. Prevention of SCD births is indisputably the most effective way of managing the long-term issue of SCD in subSaharan Africa. Newborn screening that detects SCD-affected as well as heterozygous newborns must lead to genetic counseling whenever both parents are heterozygous. However, such
information is generally provided a long time after the decision to establish a matrimonial home has been made. Effectiveness in the prevention of sickle cell births will result from the combination of two strategies: an introduction to SCD and teaching early on in school educational programs and screening followed by genetic counseling for teenagers, an age in which most wedding plans are initiated.
Research and training Studies following large cohorts of SCD patients from birth are still lacking in Africa, hampering information on key issues regarding the nature of this disease, predominantly, the main causes of SCD-related deaths, the spectrum of complications and age of onset, the psychological impact on SCD patients and their families, and the insertion issues in working life. The goal of improving survival and patient quality of life through equitable access to specific care raises questions that must be considered: what are the identifiable risk factors for occurrence of complications; how to improve blood transfusion accessibility and security; and how to promote access to protocols, including morphine and hydroxycarbamide at an affordable cost? The lack of comprehensive data on the causes of worsening anemia in SCD in sub-Saharan Africa dictates the need for further research focusing particularly on the impact of malaria and of the erythrovirus B19 in mortality due to severe anemia [30].
CONCLUSION Despite multiple constraints in sub-Saharan Africa, including building capacity for the diagnosis and management of SCD emergencies and creating structures near communities developing networks with a SCRC, it is possible that strategies based on a goal of holistic care for SCD can improve the life expectancy of patients and reduce SCD births across the continent. The success of such strategies is dependent upon the commitment of states and policies favoring innovative equal access to healthcare, a close collaboration between SCRCs of different countries and also an international commitment. Acknowledgements We acknowledge Narla Mohandas and Gil Tchernia for their advice and scientific support. Conflicts of interest There are no conflicts of interest.
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Erythroid system and its diseases
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