Current Opinion in Hematology:
ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas
Sickle cell disease in sub-Saharan Africa: stakes and strategies for control of the disease
Diallo, Dapa A.; Guindo, Aldiouma
Centre de Recherche et de Lutte contre la Drépanocytose, Bamako, Mali
Correspondence to Professor Dapa A. Diallo, Centre de Recherche et de Lutte contre la Drépanocytose, 03 BP: 186 BKO 03, Bamako, Mali. Tel: +(223) 20 22 3898; e-mail: firstname.lastname@example.org
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.
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.
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.
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 . 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.
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 between 5 and 19% of overall mortality in the population of children under 5 years of age . 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 life-threatening 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 . 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 . 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 . 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.
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 , 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, 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 .
Constraints related to patient
SCD is unfortunately considered in several sub-Saharan 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 Drépanocytose 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 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 , 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 sub-Saharan 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 .
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.
We acknowledge Narla Mohandas and Gil Tchernia for their advice and scientific support.
Conflicts of interest
There are no conflicts of interest.
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
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control; sickle cell disease; stakes; strategies; sub-Saharan Africa
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