Options for Control and Management of Inherited Hemoglobin Disorders
Even though much more work is needed on both the scientific and the economic aspects of the hemoglobinopathies, certain issues are now clear. Until more definitive ways of treating them are available, reliable knowledge exists on how they can best be managed symptomatically. Furthermore, compelling evidence suggests that population screening programs combined with prenatal diagnosis can reduce the financial burden these increasingly common diseases impose on health services. Defining several options for their control and management is therefore possible. These are based, with some modifications, on Alwan and Modell (1997).
Severe Beta Thalassemias
This list provides most of the possible options for the control and management of Beta thalassemia in developing countries.
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Option one: best possible patient care, together with retrospective genetic counseling after the first affected child is diagnosed
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Option two: best possible patient care, together with retrospective genetic counseling and the option of prenatal diagnosis for subsequent pregnancies
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Option three: best possible patient care, together with retrospective genetic counseling and prospective (premarital) carrier screening and counseling, but no prenatal diagnosis
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Option four: best possible patient care with premarital, family-based, and population-based prospective carrier screening and genetic counseling, but no prenatal diagnosis
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Option five: best possible patient care, premarital and prenatal prospective carrier screening and genetic counseling, and the option of prenatal diagnosis
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Option six: based on option four or five but includes the availability of a bone marrow transplant program.
Options one and two, though still commonly practiced in many countries, offer little prospect of reducing the frequency of serious forms of thalassemia. Overall, that reduction is best achieved by option five, which combines maximum possibilities for reducing the frequency of severe disease with the best possible care for affected children. Although thalassemia births have fallen sharply in some developed countries, the effect of prenatal screening is likely to be lower for the large mainland populations of Asia if this policy is implemented, which is why this option includes best-practice treatment. Limited studies also suggest that families that undergo prenatal diagnosis tend to settle at the population norm for the number of children that they subsequently have and that their views on their ability to have unaffected children are extremely positive. For those countries or groups in which termination of pregnancy is unacceptable for religious or cultural reasons, option four is recommended. Option six, which is possible only in countries where bone marrow transplantation is available, should be exploited by any country with a high frequency of the disease, because it offers a potentially cost-effective approach to managing some proportion of affected children.
For the extremely heterogeneous intermediate forms of Beta thalassemia, notably Hb E Beta thalassemia, options three and four would probably be best, at least until a better understanding has been gained of the clinical heterogeneity of these thalassemias.
Alpha Thalassemias
Few options are available for the Alpha° thalassemias. Homozygous babies with this condition are stillborn. However, because of the serious maternal complications of carrying these babies, this condition should be screened for prenatally, and affected babies should be identified by prenatal diagnosis with a view to terminating the pregnancy.
Hb H disease, the compound heterozygous state between Alpha+ and Alpha° thalassemia, is generally a relatively mild disorder that simply requires careful follow-up and treatment of complications. Although some have suggested that screening and prenatal diagnosis may be relevant for the more severe forms, more data are required to reach a conclusion.
Sickle Cell Disorders
These options for the management of the sickle cell disorders are directed particularly at the populations of developing countries, although, overall, they are relevant to most countries:
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Option one: best possible patient care with the use of prophylactic penicillin following diagnosis, together with retrospective genetic counseling
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Option two: best possible patient care, together with a neonatal screening program and the use of penicillin for all homozygous babies, together with retrospective screening and counseling
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Option three: best possible patient care, together with neonatal screening and the use of prophylactic penicillin from birth for homozygotes, together with population screening and prospective genetic counseling
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Option four: as for option three, plus the availability of prenatal diagnosis, bone marrow transplantation, or both.
Option three would be required to combine best management with the possibility of reducing the frequency of the disease, although whether this option would have any effect by altering the pattern of marriage is not clear. Whether prenatal screening of mothers would be valuable is also not clear: it would reduce the number of neonates who require screening, but because the cost of screening for sickle cell trait is so small, the issue is probably not important. Prenatal diagnosis can be developed (option four), but this option does not seem to be a high priority for sickling disorders in many developed countries, at least until more is known about the reasons for their phenotypic heterogeneity. By contrast, demand is greater in developing countries with limited facilities for the care of these patients. Some developed countries are beginning to immunize children with sickling disorders against infections with pneumococcus, H. influenzae, and meningococcus, but in developing countries, this treatment would add enormously to the burden of management programs. Clinical trials to test the efficacy of prophylactic penicillin with or without these vaccine regimens are urgently needed. Similarly, more information about the pathogens that cause early deaths in developing countries is required before the widespread use of prophylactic penicillin can be recommended.
Bone Marrow Transplantation
Experience in developed countries indicates that bone marrow transplantation may offer a cost-effective approach to managing a subset of patients with inherited disorders of hemoglobin (Borgna-Pignatti 1985). In developing countries, if this service is available at all, it is usually confined to the private sector or to those who can pay the fees teaching hospitals require. Given this context, defining the role of bone marrow transplantation in the global control of these diseases is difficult.
International and National Support Groups
Largely through the efforts of parents with affected children and clinicians who have taken an interest in the hemoglobin disorders, many countries have developed national thalassemia or sickle cell anemia societies that provide support for parents, workshops for doctors, and a variety of other important inputs. In the case of thalassemia, the Thalassemia International Federation acts as an international coordinating body that helps countries develop workshops for training in diagnosis and treatment and organizes international meetings at which experts from different countries share their research and clinical experiences. In 1996, a group of doctors formed the Federation des Associations de Lutte contre la Drepanocytose en Afrique (Federation of Associations to Control Sickle Cell Anemia in Africa). The membership has grown to 13 Sub-Saharan countries. The federation represents a major initiative in relation to regional training in both the diagnosis and the treatment of sickle cell disease in Sub-Saharan Africa. Unfortunately, it has been unable to raise sufficient funds to equip and run even a modest secretariat. Considering the success of the Thalassemia International Federation, particularly in countries with limited facilities for managing the hemoglobin disorders, the lack of support for this initiative in Africa is a clear indication of the importance of educating nongovernmental organizations and similar bodies about the increasing public health problems resulting from the inherited hemoglobin disorders.
Ethical and Social Issues
The various options for controlling and managing the hemoglobin disorders raise many ethical and social issues (see Weatherall and Clegg 2001b for more details). These issues arise most often in developing countries, where the level of education is often low and understanding of genetic diseases is limited. Serious genetic diseases such as thalassemia are associated with social problems such as patient stigmatization and broken marriages because one partner blames the other for the birth of an affected child. In countries where arranged marriages are still common, screening programs for heterozygotes may make it difficult for female carriers to find husbands. In addition, cultural and religious objections about interfering with nature arise when pregnancies are terminated because children have serious genetic diseases. At the same time, if governments perceive prenatal diagnosis and termination of pregnancy to be a highly cost-effective way of controlling these diseases, which they are, the danger arises that governments will pressure women to undergo these procedures. Therefore, before any programs are established, extensive discussions between governments, the medical profession, and the community about how to control these diseases are vital.
