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.

Funding

UBC PSI, Canada Research Chairs, UBC HIFI Awards, UBC 4YF, Naiman Vickars Endowment fund.

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评估检测镰状细胞病和β-地中海贫血的低成本技术：一项开放标签、国际、多中心研究

镰状细胞病（SCD）仍然是一个主要的全球健康问题，对低收入和中等收入国家（LMIC）的儿童造成了不成比例的影响。低收入和中等收入国家迫切需要准确和低成本的定点护理技术，以检测血红蛋白S （HbS）和β-地中海贫血等其他变异的携带者或疾病形式。方法在尼泊尔和加拿大进行一项开放标签、国际、多中心的临床研究。血液样本采集自健康志愿者（HbAA）和已知血红蛋白病（HbA/β-地中海贫血、HbAS、HbS/β-地中海贫血、HbSS）的参与者。六种低成本试验(常规镰状试验；HbS溶解度试验；HemoTypeSC;镰状扫描;瞪羚Hb变异试验；使用自动显微镜和机器学习的自动镰状细胞试验)与高效液相色谱（ClinicalTrials.gov标识符：NCT05506358）进行了评估。在2022年9月至2023年3月期间，我们招募了138名参与者(年龄2-74岁；（59%女性，41%男性）在尼泊尔和加拿大的临床站点。四种低成本的检测方法（haemtypesc、Sickle SCAN、Gazelle和自动镰刀）能够准确地检测出严重的SCD （HbSS、HbS/β-地中海贫血）(灵敏度>；96%；特异性的在99%)。相比之下，对于携带者形式，血型esc和镰刀扫描仅检测到HbAS(灵敏度>；97%；特异性100%)，而不是HbA/β-地中海贫血(敏感性0%；Gazelle检测HbAS（灵敏度100%，特异性100%）和HbA/β-地中海贫血（灵敏度91%，特异性99%），自动镰刀试验检测两种性状条件(HbA和HbA/β-地中海贫血；灵敏度85%，特异性85%)。当HbS与β-地中海贫血共存时，Gazelle和自动镰状试验能准确识别严重的SCD和携带者形式。然而，haemtypesc和Sickle SCAN遗漏了β-地中海贫血的特征，需要与其他低成本的测试相补充。资助：bc PSI，加拿大研究主席，UBC HIFI奖，UBC 4YF， Naiman Vickars捐赠基金。

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来源期刊

The Lancet regional health. Southeast Asia

CiteScore

2.20

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0.00%

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