Newborn Screening for Sickle Cell Disease Among Tribal Populations in the States of Gujarat and Madhya Pradesh in India: Evaluation and Outcome Over 6 Years.

Sickle cell disease (SCD) poses considerable public health problems in India. This study was undertaken to understand the clinical course of SCD among children identified during newborn screening programmes in Gujarat and Madhya Pradesh where the frequency of the HbS gene is high. A total of 8,916 newborn babies 8,411 from Gujarat and 505 from Madhya Pradesh were screened over 6 years (2010-2016) using HPLC and the diagnosis was confirmed by molecular analysis in a subset. A total of 128 babies (122 Gujarat, 6 Madhya Pradesh) were identified with sickle cell disease, of whom 87 (69 HbSS, 18 HbS-ß thalassemia) from Gujarat were followed for 0.5-6.6 years. Acute painful events, severe anemia and fever with infections were the major complications and 23 babies required hospitalization. Severe to moderate clinical presentation was found in 13.8% babies with SCD whereas, 86.2% babies had a milder presentation. Presence of ameliorating factors (α-thalassemia and Xmn 1 polymorphism) did not have a discernible effect on the clinical severity. Parents of babies with SCD were educated and counseled for home care. Distribution of mobile phones to 44 families having babies with SCD was beneficial as it allowed regular contact with patients and their families. Genetic counseling to the affected families has increased the awareness and acceptance for prenatal diagnosis and 18 couples opted for prenatal diagnosis in subsequent pregnancies. SCD is not always mild among tribal groups in India. Therefore, facilities for early diagnosis and prophylactic treatment in the tertiary care centers should be made available. The difficulties in regular follow up of the babies in remote rural areas have also been highlighted.

Multicenter Evaluation of HemoTypeSC as a Point-of-Care Sickle Cell Disease Rapid Diagnostic Test for Newborns and Adults Across India.

OBJECTIVES: Sickle cell anemia is the commonest genetic disorder in India, and the frequency of the sickle cell gene is very high in the remote tribal areas where facilities are generally limited. Therefore, a rapid and affordable point-of-care test for sickle cell disease is needed. METHODS: The diagnostic accuracy of HemoTypeSC was evaluated against automated high-performance liquid chromatography (HPLC) as the gold standard for its efficacy in a newborn screening program. RESULTS: A total of 1,559 individuals (980 newborns and 579 adults) from four participating centers were analyzed by both methods. HemoTypeSC correctly identified 209 of 211 total hemoglobin (Hb) SS cases, for a 99.1%/99.9% total HbSS sensitivity/specificity. Overall, HemoTypeSC exhibited sensitivity and specificity of 98.1% and 99.1% for all possible phenotypes (HbAA, HbAS, and HbSS) detected. HPLC is relatively expensive and not available in most laboratories in remote tribal areas. CONCLUSIONS: We conclude that the rapid, point-of-care testing device HemoTypeSC test is suitable for population and newborn screening for the HbS phenotype.

Feasibility of a newborn screening and follow-up programme for sickle cell disease among South Gujarat (India) tribal populations.

OBJECTIVES: To evaluate the feasibility of a newborn screening and follow-up programme for sickle cell disease (SCD) among tribal populations of south Gujarat, India. METHODS: A total of 5467 newborn babies were screened over 2 years using High-performance liquid chromatography, with diagnosis by molecular analysis. The SCD babies were followed-up clinically and haematologically regularly for 1.5 to 5 years to describe the course of the disease. RESULTS: Thirty-three babies (0.60%) were sickle homozygous, 13 (0.23%) were-sickle-ß-thalassaemia, 687 (12.5%) were sickle heterozygous, and 4736 were unaffected. The parents of SCD babies were educated and counselled for home care. There were 32 babies (69.5%) who could be clinically and haematologically followed-up; 7 babies (21.8%) presented with severe clinical complications, whereas 18 (56.2%) babies were asymptomatic till the last follow-up. The variation in clinical presentation was seen in spite of the presence of ameliorating factors, such as high fetal haemoglobin, Xmn-I polymorphism, and α-thalassaemia. CONCLUSION: In addition to demonstrating the possibility of establishing a newborn screening programme for sickle cell disorders among tribal populations, this study has shown that the disease is not always mild among tribal groups in India, as previously believed. There is a need, therefore, for increasing awareness among these tribal groups about the disease, and for regular monitoring of affected babies to reduce morbidity and mortality and to understand the natural course of the disease.

Transfusion in sickle cell disease: experience from a Gujarat centre.

OBJECTIVES: Following impressions that the use of blood transfusion in sickle cell disease may be inappropriately high, transfusion practice at a major blood bank in an area of high prevalence of sickle cell disease was assessed. METHODS: Retrospective review of blood usage in sickle cell disease at a major blood bank in south Gujarat in 2010 was conducted with prospective more detailed data collection over 18 wk period (April 7 through August 15) in 2011. The results were compared with transfusion usage in the Jamaican Sickle Cell Clinic. RESULTS: In 2010, this blood bank processed a total of 19,037 units of which 384 (5.2 %) units were for patients with sickle cell disease. Median transfusion use was 1 unit but 16 patients (4.2 %) of those transfused received 10 units or more and five patients received over 20 units. More detailed prospective analysis revealed that most transfusions occurred between ages 5-15 y, 40 % of subjects had pretransfusion hemoglobin levels below 6 g/dL, symptoms were generally vague such as fever, bone pain, weakness and that 26 % denied any specific symptoms. CONCLUSIONS: Transfusion usage greatly exceeds that in the Jamaican Sickle Cell Clinic. Transfusion therapy carries risks and cost and more detailed investigation and diagnosis of anemic episodes is necessary to define the role of transfusion among other potential therapies. Eventually, guidelines evolved by Indian specialists should determine the indications for transfusion in sickle cell disease.

Distribution of beta-globin haplotypes among the tribes of southern Gujarat, India.

The present study was carried out in Indo-European speaking tribal population groups of southern Gujarat (India) to elucidate the allelic and haplotypic content of ß-globin system in individuals with HbAA genotypes. 6 neutral restriction sites of the ß-globin system were analysed and various statistical parameters were estimated to draw meaningful interpretations. All the 6 sites were found to be polymorphic and most were in Hardy-Weinberg Equilibrium in the studied group. Haplotypes were constructed using two different combinations of the 6 restriction sites analysed. Analysis of the 5 sites revealed a set of three predominant haplotypes, '+----', '-++-+' and '-+-++'; and haplotypes '+--', '++-' and '+++' were found to be the most frequent when the 3 sites were used to construct the haplotypes. Haplotypic heterozygosity levels (>83%) observed in the present study group were comparable to those observed in African and Afro-American populations and greater than other world populations. All the ancestral haplotypes, +-----, -++-+, -+-++ and ----+ were found in the study group. The distribution pattern of various haplotypes was consistent with the global pattern. The paucity of comparable data from other Indian populations restricted one from making interpretations about the study group's relationships with other Indian populations but the results were indicative of older population histories or experience of gene flow by the study group and their affinities with populations of southern India.