Genetic epidemiology of beta-thalassemia in the Maldives: 23 years of a beta-thalassemia screening program

Abstract

The Maldives is an archipelago of 407,660 people according to population census of 2014, made up of 20 atolls, which has one of the highest prevalence of β-thalassemia worldwide. However, there is a dearth of studies related to β-thalassemia in the Maldives; therefore, in this study, we aimed to investigate the genetic epidemiology of β-thalassemia in Maldives. Blood samples were collected from 110,504 participants (1992–2015). Hemoglobin and RBC indices were measured on automated hematology analyzers. The quantitation of hemoglobin, HbA2, Hb F, and other abnormal Hb variants were assessed by HPLC. Molecular analysis was performed for the most common mutations in Southeast Asia for only 874 individuals either heterozygous or homozygous for these mutations using reverse dot blot hybridization. We screened 110,504 individuals for β-thalassemia between 1992 and 2015, which is ~ 30% of the entire population. The β-thalassemia carrier frequency was estimated to be 16.2%. Molecular diagnosis of 874 β-thalassemia carriers/major was performed for the most common seven mutations in Southeast Asia; of these, 139 patients were diagnosed as β-thalassemia major. This analysis showed that the most common mutations were IVS1 + 5G > C, (678; 77.6%), followed by the CD 30 (136; 15.6%). The least frequent mutation was FS8/9, (1, 0.001%), followed by IVS1 + 1G > T and CD15 (2; 0.2%). The frequency of β-thalassemia varies significantly among the 20 different atolls in Maldives. This study is expected to improve genetic counseling, creating awareness, enhance premarital screening, nd customize the prevention and treatment strategies based on the needs of each atoll. https://www.sciencedirect.com/science/article/abs/pii/S0378111920302134

Maldives World “hot spot” for Thalassemia

Maldives is a world ‘hot spot’ for thalassemia. The prevalence of b-thalassemia in the population of this country is 18.1%; 1 in 5 people are carriers of the disease and 1 in 120 live births are estimated to be thalassemia majors. Currently, there are more than 700 thalassemia major patients who require regular blood transfusions, and as a result, 60% of the blood utilization of the Maldives treats these patients.

Importance of transfusion medicine in Maldives

Over the past many years I have been impressed by the prevalence of blood dyscrasias In Maldives. Reduced levels of hemoglobin are common among all the Maldivians and the consequences thereof seem to be a household story. Then there are various blood cancers, many bleeding disorders and such prevalent hereditary disorders as thalassaemias, sickle cell anemias, and enzyme deficiencies. In the comparative analysis of diseases, it is obvious that blood diseases are the commonest ailments in man. This is compounded by the fact that abnormalities in blood are encountered as an important secondary manifestation in large number of non-haematological disorders.

At educational level in the Maldives there is no degree college, medical school or university where structured courses in Haematology are offered at any level. Yet haematological investigations account for almost 40 % of the laboratory workload. The irony is that there are no personnel specifically trained in the field of Haematology and specifically Immunohaematology to handle this workload. This also includes Blood transfusion services where an error may cost a patient his life.

The Haematology Department should provide comprehensive laboratory services for the diagnosis and management of both haematological and oncological disorders. Most of the routine haematology and coagulation tests have to be performed in the laboratory. Specialist laboratory services should be established in the Haematology laboratories include immunophenotyping of leukaemia and lymphoma, thrombophilic screening, coagulation factor assays, platelet function tests, bone marrow culture and special assays such as those for vitamin B12, erythropoietin and red cell enzymes.

Transfusion/Immunohaematology services are also controlled by the Haematology Department. As well as providing the routine services of blood grouping, cross matching and the issuing of various blood products, the Transfusion/Immunohaematology section plays an important role in the diagnosis and treatment of immunohaematological disorders, such as haemolytic disease of the newborn, and in the management of haemophilia and thalassaemia major.

Though the above-mentioned things have to be there with in the infrastructure of health system for the management of blood disorders in the Maldives. We don’t have enough locals who has been trained in the following field to meet the demand to establish a National blood bank. This is of special interest to the Maldives as the incidence of Thalassaemia is one of the highest in the world. Prevalence of Thalassaemia in the Maldives is about 18.5% of the whole population, which is perhaps the highest in the world.

There are about 600 registered thalassaemia major patients in National Thalassaemia Center in the capital Male’ where they receive regular blood transfusions. These patients they require only packed erythrocytes to correct the deficiency of hemoglobin. Yet we are unable to provide them these blood components in appropriate manner due to unavailability of equipments and lack of personnel. Blood component therapy is the modern concept of administration of blood and blood products. It is aimed at providing specific blood components for specific deficiency states effectively, economically and with greater safety. The procedures are easy to adopt, provided the technical know how for fractionation of blood.

Component therapy enhances the number of users without the need of increasing the demand on blood supply. With modest fractionation one unit of fresh whole blood can now be used by at least four different recipients; more can be benefited with further fractionation. Blood component therapy also protects the recipients from the risks, which are inherent in whole blood transfusions.

I have found Immunohaematology or Transfusion Medicine is an important field to a country like Maldives where the prevalence of blood diseases are extremely high. Therefore it is mandatory to train qualified people in this field for the national interest and for the betterment of family health.