Evaluation of low-cost techniques to detect sickle cell disease and β-thalassemia: an open-label, international, multicentre studyResearch in context

Summary: Background: Sickle cell disease (SCD) persists as a major global health problem, disproportionately affecting children in low- and middle-income countries (LMIC). Accurate and low-cost point-of-care techniques are urgently needed in LMIC to detect carrier or disease forms with haemoglobin...

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Main Authors: Pranav Shrestha, Hendrik Lohse, Christopher Bhatla, Heather McCartney, Alaa Alzaki, Navdeep Sandhu, Pardip Kumar Oli, Sanjeev Chaudhary, Ali Amid, Rodrigo Onell, Nicholas Au, Hayley Merkeley, Videsh Kapoor, Rajan Pande, Boris Stoeber
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:The Lancet Regional Health - Southeast Asia
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772368225000423
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Summary:Summary: Background: Sickle cell disease (SCD) persists as a major global health problem, disproportionately affecting children in low- and middle-income countries (LMIC). Accurate and low-cost point-of-care techniques are urgently needed in LMIC to detect carrier or disease forms with haemoglobin S (HbS) and other variants like β-thalassemia. Methods: An open-label, international, multicentre study was conducted at clinical sites in Nepal and Canada. Blood samples were collected from healthy volunteers (HbAA) and participants with known haemoglobinopathies (HbA/β-thalassemia, HbAS, HbS/β-thalassemia, HbSS). The performance of six low-cost tests (Conventional sickling test; HbS solubility test; HemoTypeSC; Sickle SCAN; Gazelle Hb variant test; Automated sickling test using automated microscopy and machine learning) was evaluated against HPLC (ClinicalTrials.gov Identifier: NCT05506358). Findings: Between September 2022 and March 2023, we enrolled 138 participants (aged 2–74 years; 59% female, 41% male) at clinical sites in Nepal and Canada. Four low-cost tests (HemoTypeSC, Sickle SCAN, Gazelle, and automated sickling), which could identify phenotypes, detected severe SCD (HbSS, HbS/β-thalassemia) accurately (sensitivity >96%; specificity >99%). In contrast, for carrier forms, HemotypeSC and Sickle SCAN only detected HbAS (sensitivity >97%; specificity 100%) and not HbA/β-thalassemia (sensitivity 0%; specificity 100%), while Gazelle detected HbAS (sensitivity 100%, specificity 100%) and HbA/β-thalassemia (sensitivity 91%, specificity 99%), and automated sickling test detected both trait conditions (HbAS and HbA/β-thalassemia; sensitivity 85%, specificity 85%). Interpretation: When HbS co-exists with β-thalassemia, Gazelle and automated sickling test accurately identify severe SCD and carrier forms. However, HemotypeSC and Sickle SCAN miss β-thalassemia trait, and need to be complemented with other low-cost tests. Funding: UBC PSI, Canada Research Chairs, UBC HIFI Awards, UBC 4YF, Naiman Vickars Endowment fund.
ISSN:2772-3682