Large Scale Community-Based Sickle Cell Surveillance in an Aboriginal Population from Western India

Sickle cell disease (SCD) is an inherited blood disorder that affects millions of people worldwide. The Government of India has initiated the “Sickle Cell Elimination Mission,” owing to the significant burden of SCD among its aboriginal (tribal) populations. We designed our study in alignment with this national initiative to implement a comprehensive screening program in tribal communities of India. The study aimed to determine the prevalence of SCD and sickle cell trait (SCT) amongst aboriginal communities in Nandurbar district in Western India. The primary objective was to develop a robust community-level screening methodology with geotagging of the affected individuals for long-term follow-up. The secondary objective was to study the clinical phenotype and health-related quality of life (HR-QoL) of the newly diagnosed SCD individuals. This was an observational study in the Aboriginal tribal district of Western India along the Satpura ranges encompassing community-level screening of 344,374 individuals from Nov 2023, to Mar 2024, spending 208,800 man-hours in area covering 2299 square miles (sq-mi), with a population density of 700/sq-mi. The population screened belonged to remote locales with minimal access to health care (1 doctor/ 9000 populace) and had never undergone sickle screening or received care for SCD earlier. The population faced extreme disadvantages, with 69% belonging to aboriginal tribes and the majority being functionally illiterate (59.3%). Of those approached for screening, 46.87% (161,400) agreed to get tested. Those tested came from 646 schools/ colleges (n-130483), 284 villages/ hamlets (n-19082), and 196 visits to primary health centers/ rural hospitals/ District hospitals (n-9399), including 2436 pregnancies (472 antenatal, 1964 postnatal cases) through door-to-door visits. Demographic details, medical history, and blood samples were collected followed by a thorough medical examination after obtaining informed consent. Hemoglobin (Hb) electrophoresis was performed at an on-site lab using capillary zone electrophoresis (CZE) (average 1390 tests/day). The data was collated using custom-built software by the primary author, available as care4sickle.in and on Google Play Store as “care4sickle” with level 4 security and is HIPAA compliant. The software is intuitive and designed for children and the functionally illiterate using pictorial representation. The hybrid application was available in multiple local languages (3), including English. The QoL was analyzed using validated WHOQOL-BREF and SF-36 Questionnaire in the local language. Genetic counseling was done through community partnerships and community health care workers. The data was analyzed using JMP ver. 17.2.0. The prevalence of SCD was 8.68% (n-1402), and SCT was 15.23% (n-24577), with 0.16% (n-264) individuals having compound heterozygosity. Incidentally, 5.27% (n-8501) had other hemoglobinopathies. Geotagging revealed a heatmap identifying high prevalence zones among specific ethnicities and geographical locations. Mathematical modeling based on pedigree charting and positivity rates on family screening revealed a possibility of 2.84x positivity for sickle syndrome (SCT/ SCD) for every newly diagnosed SCD. The SCD individuals had transfusion requirement of 15.6/1000 patient-years, mean Hb 9.6±0.1g/dL without transfusions, mean HbF of 22.4±7.5%, low HbA2 with normal red cell indices in 32.88%, palpable splenomegaly in 58.48% with a mean size of 3.6±2.4cm, crises and pain episodes (VAS>5) of 1.92 and 112/1000 patient-years respectively. The domain-wise median score (IQR) of WHOQoL-BREF of SCD individuals for physical health was 56 (19), psychological was 56(25), social relationship was 69(19), and environmental domain was 63(13); whereas for SF-36 was 75(25) for physical function, 0(75) for role limitations due to physical health, 0(100) for role limitations due to emotional problems, 55(28) for energy/ fatigue, 64(20) for emotional well-being, 62.5(37.5) for social functioning, 67.5(45) for pain, and 45(35) for general health. We have demonstrated the feasibility of large-scale community screening for SCD in a population facing extreme socio-economic deprivation. Individuals detected to have SCD were found to have high rates of splenomegaly, High HbF/ Hb, limited history of painful episodes or other disease complications, and QOL within population norms.