Shrestha Pranav, Lohse Hendrik, Bhatla Christopher, McCartney Heather, Alzaki Alaa, Sandhu Navdeep, Oli Pardip Kumar, Chaudhary Sanjeev, Amid Ali, Onell Rodrigo, Au Nicholas, Merkeley Hayley, Kapoor Videsh, Pande Rajan, Stoeber Boris
Department of Mechanical Engineering, The University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, British Columbia, V6T 1Z4, Canada.
Department of Mathematics and Computer Science, Eindhoven University of Technology, Groene Loper 3, 5612 AE, Eindhoven, the Netherlands.
Lancet Reg Health Southeast Asia. 2025 Mar 29;35:100571. doi: 10.1016/j.lansea.2025.100571. eCollection 2025 Apr.
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.
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).
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%).
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.
UBCPSI, Canada Research Chairs, UBC HIFI Awards, UBC 4YF, Naiman Vickars Endowment fund.
镰状细胞病（SCD）仍然是一个重大的全球健康问题，对低收入和中等收入国家（LMIC）的儿童影响尤为严重。低收入和中等收入国家迫切需要准确且低成本的即时检测技术，以检测携带血红蛋白S（HbS）的携带者或疾病形式以及其他变体，如β地中海贫血。
在尼泊尔和加拿大的临床地点进行了一项开放标签、国际多中心研究。从健康志愿者（HbAA）和已知血红蛋白病的参与者（HbA/β地中海贫血、HbAS、HbS/β地中海贫血、HbSS）中采集血样。针对高效液相色谱法（ClinicalTrials.gov标识符：NCT05506358）评估了六种低成本检测方法（传统镰变试验；HbS溶解度试验；HemoTypeSC；Sickle SCAN；瞪羚血红蛋白变体检测；使用自动显微镜和机器学习的自动镰变试验）的性能。
在2022年9月至2023年3月期间，我们在尼泊尔和加拿大的临床地点招募了138名参与者（年龄2 - 74岁；59%为女性，41%为男性）。四种能够识别表型的低成本检测方法（HemoTypeSC、Sickle SCAN、瞪羚检测和自动镰变检测）能够准确检测出重度SCD（HbSS、HbS/β地中海贫血）（敏感性>96%；特异性>99%）。相比之下，对于携带者形式，HemoTypeSC和Sickle SCAN仅能检测出HbAS（敏感性>97%；特异性100%），而无法检测出HbA/β地中海贫血（敏感性0%；特异性100%），而瞪羚检测能够检测出HbAS（敏感性100%，特异性100%）和HbA/β地中海贫血（敏感性91%，特异性99%），自动镰变检测则能检测出两种特征情况（HbAS和HbA/β地中海贫血；敏感性85%，特异性85%）。
当HbS与β地中海贫血共存时，瞪羚检测和自动镰变检测能够准确识别重度SCD和携带者形式。然而，HemoTypeSC和Sickle SCAN会遗漏β地中海贫血特征，需要用其他低成本检测方法进行补充。
加拿大英属哥伦比亚大学精准健康科学研究所、加拿大研究主席计划、英属哥伦比亚大学高影响力基金奖、英属哥伦比亚大学4YF基金、奈曼·维克斯捐赠基金。
