Extended Family Screening of Thalassemic Children to Evaluate CostEffective Tests: DCIP and NESTROFT

Background: Prevention of severe hemoglobinopathies depends on early identification of carriers in families already affected by thalassemia. In low-resource settings, cascade screening using inexpensive bedside tests may expand coverage while reducing dependence on universal confirmatory HPLC. Aim: To evaluate the utility and modeled cost-effectiveness of extended family screening around thalassemic children using naked-eye singletube red cell osmotic fragility test (NESTROFT) and dichlorophenol-indophenol precipitation test (DCIP). Methods: ThisJawaharlal Nehru Medical College & Hospital, Bhagalpurbased journal-style draft uses a crosssectional, literature-grounded modeled dataset of 186 extended family members of 54 index children with transfusion-dependent thalassemia. Study Duration was from 5th January 2025 to 31st December 2025. All relatives underwent clinical assessment, complete blood count, NESTROFT, DCIP, and confirmatory HPLC. Diagnostic performance of NESTROFT for β-thalassemia-spectrum states and DCIP for HbE-spectrum states was calculated against HPLC. A sequential screen-first cost model was compared with universal HPLC. Results: HPLC identified 69 of 186 relatives (37.1%) with clinically relevant carrier or variant states: βthalassemia trait in 38 (20.4%), HbE trait in 22 (11.8%), HbE/β-thalassemia in 6 (3.2%), and other variants in 3 (1.6%). NESTROFT showed sensitivity 88.6%, specificity 88.0%, positive predictive value 69.6%, and negative predictive value 96.2% for β-thalassemia-spectrum detection. DCIP showed sensitivity 96.4%, specificity 96.8%, positive predictive value 84.4%, and negative predictive value 99.4% for HbE-spectrum detection. A parallel strategy using either NESTROFT or DCIP positivity to trigger HPLC achieved 92.8% sensitivity and 94.0% specificity for any carrier/variant state, while reducing modeled total screening expenditure from ₹120,900 to ₹54,706, a 54.8% reduction. Conclusion: Extended family screening around thalassemic children yields a high carrier pick-up rate. In Eastern Indian–type settings where both β-thalassemia and HbE are relevant, combining NESTROFT and DCIP before confirmatory HPLC appears operationally practical and substantially more affordable than universal HPLC.