Sickle haemoglobin comes of age
Authors: Graham Serjeant
Journal: The Lancet Global Health (2014)

Long marginalised as a disorder confined to specific racial groups, sickle-cell disease is now assuming its rightful place as a major global public health problem. Most patients in the Americas, the Caribbean, and much of Europe have been of one racial group, which led to the common misconception that the disease was confined to people of African origin. Indeed, the mutation causing sickle haemoglobin (HbS) was noted on at least three separate occasions in Africa, and the associated polymorphisms are named after the regions where they were first described: Benin, Bantu, and Senegal.1Pagnier J Mears JG Dunda-Belkhodja O et al.Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa.Proc Natl Acad Sci USA. 1984; 81: 1771-1773Crossref PubMed Scopus (336) Google Scholar A fourth independent occurrence of the HbS gene is shared by people around the Gulf and in India where the prevalence of the trait exceeds 25% in many populations. The relative protection against falciparum malaria conferred by the HbS gene during a critical period of early childhood ensured a survival advantage and increasing prevalence over the generations. From this primary distribution, the gene was carried from west and central Africa to the Americas by the African slave trade, and latterly by voluntary migration mostly to the UK and Europe. The extent and speed of this migration is the subject of an investigation by Frédéric Piel and colleagues in The Lancet Global Health.2Piel FB Tatem AJ Huang Z Gupta S Williams TN Weatherall DJ Global migration and changing distribution of sickle haemoglobin: a quantitative study of temporal trends between 1960 and 2000.Lancet Glob Health. 2013; (published online Jan 14.)http://dx.doi.org/10.1016/S2214-109X(13)70150-5Google Scholar The investigators combined data from the World Bank's Global Bilateral Migration Database of 232 countries with known HbS allele frequencies in the countries from which migration takes place and concluded that migration of individuals with HbS increased from 1·6 million in 1960, to 3·6 million in 2000. The analyses are elegant but assume homogeneity in the distribution of the HbS gene in the donor countries, which might be broadly true in Nigeria, but not in countries such as Uganda and India, in which exist substantial tribal variations in trait frequency. In India, the HbS gene is widespread across Gujarat, Madhya Pradesh, Maharashtra, Chhattisgarh, and Odisha in central India, with a second focus in the north of Tamil Nadu and Kerala in southern India, reaching HbS frequencies as high as 35%; however, the trait is largely confined to the original tribal people living on the Deccan plateau, few of whom will participate in the emigration that traditionally takes place from major cities around the coast. Notwithstanding these fairly minor concerns, an important implication of Piel and colleagues' findings is that clinical services for patients will need to be greatly increased in countries with existing expertise, and developed in others without existing services. The structure of these clinical services will be established by local awareness, resources, and expertise. India again has shown that much can be achieved with political will, despite restricted resources, and three states in central India—Gujarat, Maharashtra, and Chhattisgarh—already have sickle-cell control programmes, which have focused largely on population screening and monetary support. The mode of delivery of optimum care is still debated, but there are advantages in dedicated centres providing continuity of care, which can avoid the disruption of transition from paediatric to adult care3Jordan L Swerdlow P Coates TD Systematic review of transition from adolescent to adult care in patients with sickle cell disease.J Pediatr Hematol Oncol. 2013; 35: 165-169Crossref PubMed Scopus (58) Google Scholar during which many patients default from regular monitoring just as serious problems such as painful crises, leg ulceration, delayed growth and puberty, priapism, and pregnancy are emerging. Furthermore, a holistic approach to management has advantages, encouraging patients to attend earlier and reducing morbidity.4Akinyanju OO Otaigbe AI Ibidapo MO Outcome of holistic care in Nigerian patients with sickle cell anaemia.Clin Lab Haematol. 2005; 27: 195-199Crossref PubMed Scopus (30) Google Scholar The organisation of appropriate clinical services will need specialist expertise and training that could have been impeded by the absence of career structures in the specialty of non-malignant haematology. Debate even surrounds the most appropriate training for health-care personnel in sickle cell, on the basis that the required expertise is multidisciplinary, including infectious disease, pain management, psychosocial, and family counselling, and informed nurses or counsellors can have an important role for patients who often just need to discuss problems. Other objectives in management involve prevention of serious complications, but also of the disease itself. Although presently incurable, much can be done to reduce morbidity and mortality from sickle-cell disease; because the greatest mortality is in the latter half the first year,4Akinyanju OO Otaigbe AI Ibidapo MO Outcome of holistic care in Nigerian patients with sickle cell anaemia.Clin Lab Haematol. 2005; 27: 195-199Crossref PubMed Scopus (30) Google Scholar early diagnosis is essential, preferably at birth. This finding has led to the introduction of screening of newborn babies for sickle-cell disease, which is universal in the USA and the UK, and focused in perceived high-risk groups in France; Brazil; Ontario, Canada; and the Caribbean. Once diagnosed, patients are monitored in specialised clinics and the family are made aware that the first clinical manifestation might be life-threatening. The other challenge will be in the education of patients and carriers about the genetics and prevention of the disease. Sickle-cell disease results from the inheritance of abnormal genes from both parents and can be avoided if one parent has a normal (AA) haemoglobin genotype; the haemoglobin genotype then becomes one of many factors influencing their choice of partner. By contrast with a huge amount of scientific literature addressing the pathophysiology, risk factors, and treatment of clinical manifestations of the disease, there is a dearth of epidemiology, which could contribute to our understanding, and Piel and colleagues' article hints at the potential power of such approaches to the disease. Despite some daunting statistics in their report, a clear message is the need to define and provide optimum clinical services for patients, screening of newborn babies in countries where this is not yet available, and educational programmes that offer haemoglobin genotype detection and provide appropriate non-directional counselling. Such expertise is already available and can be drawn on by countries needing to develop these services anew. The rapidly changing genetic pattern of populations and the spread of the HbS gene from accelerating emigration demands services, but will also contribute positively to the cultural diversity of many societies. I declare that I have no conflicts of interest. Global migration and the changing distribution of sickle haemoglobin: a quantitative study of temporal trends between 1960 and 2000Global human population movements have had a substantial effect on the distribution of the HbS gene. Population movements can create a long-term burden on health-care systems. Our findings, which emphasise countries in which migration fluxes are changing the most, should increase awareness about the global burden of haemoglobinopathies and encourage policy makers to implement specific public health interventions, such as screening programmes and genetic counselling. Full-Text PDF Open Access