BACKGROUND To reduce the risk of drug-induced haemolysis, all patients should be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) prior to prescribing primaquine (PQ)-based radical cure for the treatment of vivax malaria. This systematic review and individual patient meta-analysis assessed the utility of a qualitative lateral flow assay from Access Bio/CareStart (Somerset, NJ) (CareStart Screening test for G6PD deficiency) for the diagnosis of G6PDd compared to the gold standard spectrophotometry (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42019110994). METHODS AND FINDINGS Articles published on PubMed between 1 January 2011 and 27 September 2019 were screened. Articles reporting performance of the standard CSG from venous or capillary blood samples collected prospectively and considering spectrophotometry as gold standard (using kits from Trinity Biotech PLC, Wicklow, Ireland) were included. Authors of articles fulfilling the inclusion criteria were contacted to contribute anonymized individual data. Minimal data requested were sex of the participant, CSG result, spectrophotometry result in U/gHb, and haemoglobin (Hb) reading. The adjusted male median (AMM) was calculated per site and defined as 100% G6PD activity. G6PDd was defined as an enzyme activity of less than 30%. Pooled estimates for sensitivity and specificity, unconditional negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated comparing CSG results to spectrophotometry using a random-effects bivariate model. Of 11 eligible published articles, individual data were available from 8 studies, 6 from Southeast Asia, 1 from Africa, and 1 from the Americas. A total of 5,815 individual participant data (IPD) were available, of which 5,777 results (99.3%) were considered for analysis, including data from 3,095 (53.6%) females. Overall, the CSG had a pooled sensitivity of 0.96 (95% CI 0.90-0.99) and a specificity of 0.95 (95% CI 0.92-0.96). When the prevalence of G6PDd was varied from 5% to 30%, the unconditional NPV was 0.99 (95% CI 0.94-1.00), with an LR+ and an LR- of 18.23 (95% CI 13.04-25.48) and 0.05 (95% CI 0.02-0.12), respectively. Performance was significantly better in males compared to females (p = 0.027) but did not differ significantly between samples collected from capillary or venous blood (p = 0.547). Limitations of the study include the lack of wide geographical representation of the included data and that the CSG results were generated under research conditions, and therefore may not reflect performance in routine settings. CONCLUSIONS The CSG performed well at the 30% threshold. Its high NPV suggests that the test is suitable to guide PQ treatment, and the high LR+ and low LR- render the test suitable to confirm and exclude G6PDd. Further operational studies are needed to confirm the utility of the test in remote endemic settings.

中文翻译：

---

用于检测 6-磷酸葡萄糖脱氢酶缺乏症的 Access Bio/CareStart 快速诊断测试的性能：系统评价和荟萃分析。

背景 为降低药物引起的溶血风险，在开出基于伯氨喹 (PQ) 的根治疗法治疗间日疟疾之前，应检测所有患者是否存在葡萄糖-6-磷酸脱氢酶 (G6PD) 缺乏症 (G6PDd)。该系统回顾和个体患者荟萃分析评估了 Access Bio/CareStart（新泽西州萨默塞特）（CareStart G6PD 缺乏症筛查试验）与金标准分光光度法（国际前瞻系统评价登记册 [PROSPERO]：CRD42019110994）。方法和结果 筛选了 2011 年 1 月 1 日至 2019 年 9 月 27 日期间在 PubMed 上发表的文章。文章报告了前瞻性收集的静脉或毛细血管血样中标准 CSG 的性能，并将分光光度法视为金标准（使用来自爱尔兰威克洛的 Trinity Biotech PLC 的试剂盒）。与符合纳入标准的文章作者联系以提供匿名的个人数据。要求的最少数据是参与者的性别、CSG 结果、U/gHb 分光光度法结果和血红蛋白 (Hb) 读数。调整后的男性中位数 (AMM) 按站点计算并定义为 100% G6PD 活动。G6PDd 被定义为小于 30% 的酶活性。敏感性和特异性的汇总估计、无条件阴性预测值 (NPV)、阳性似然比 (LR+)、使用随机效应双变量模型将 CSG 结果与分光光度法进行比较，计算出负似然比 (LR-) 和负似然比 (LR-)。在 11 篇符合条件的已发表文章中，有 8 项研究提供了个别数据，其中 6 项来自东南亚，1 项来自非洲，1 项来自美洲。共有 5,815 个个体参与者数据 (IPD) 可用，其中 5,777 个结果 (99.3%) 被考虑用于分析，包括来自 3,095 (53.6%) 名女性的数据。总体而言，CSG 的汇总敏感性为 0.96（95% CI 0.90-0.99），特异性为 0.95（95% CI 0.92-0.96）。当 G6PDd 的患病率在 5% 到 30% 之间变化时，无条件 NPV 为 0.99 (95% CI 0.94-1.00)，LR+ 和 LR- 分别为 18.23 (95% CI 13.04-25.48) 和 0.05 (95% CI 0.02-0.12）。与女性相比，男性的表现明显更好 (p = 0. 027)，但从毛细血管或静脉血中采集的样本之间没有显着差异 (p = 0.547)。该研究的局限性包括所包含数据缺乏广泛的地理代表性，并且 CSG 结果是在研究条件下产生的，因此可能无法反映常规环境中的表现。结论 CSG 在 30% 的阈值下表现良好。其高 NPV 表明该测试适合指导 PQ 治疗，高 LR+ 和低 LR- 使测试适合确认和排除 G6PDd。需要进一步的操作研究来确认该测试在偏远地方病环境中的实用性。该研究的局限性包括所包含数据缺乏广泛的地理代表性，并且 CSG 结果是在研究条件下产生的，因此可能无法反映常规环境中的表现。结论 CSG 在 30% 的阈值下表现良好。其高 NPV 表明该测试适合指导 PQ 治疗，高 LR+ 和低 LR- 使测试适合确认和排除 G6PDd。需要进一步的操作研究来确认该测试在偏远地方病环境中的实用性。该研究的局限性包括所包含数据缺乏广泛的地理代表性，并且 CSG 结果是在研究条件下产生的，因此可能无法反映常规环境中的表现。结论 CSG 在 30% 的阈值下表现良好。其高 NPV 表明该测试适合指导 PQ 治疗，高 LR+ 和低 LR- 使测试适合确认和排除 G6PDd。需要进一步的操作研究来确认该测试在偏远地方病环境中的实用性。高 LR+ 和低 LR- 使测试适合确认和排除 G6PDd。需要进一步的操作研究来确认该测试在偏远地方病环境中的实用性。高 LR+ 和低 LR- 使测试适合确认和排除 G6PDd。需要进一步的操作研究来确认该测试在偏远地方病环境中的实用性。