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

IF 5 Q1 HEALTH CARE SCIENCES & SERVICES

The Lancet regional health. Southeast Asia Pub Date : 2025-03-29 DOI:10.1016/j.lansea.2025.100571

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

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Abstract

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.