Hawkes Michael, Conroy Andrea L, Opoka Robert O, Namasopo Sophie, Liles W Conrad, John Chandy C, Kain Kevin C
Department of Medicine, University of Toronto, Toronto, Canada.
Malar J. 2014 Feb 1;13:43. doi: 10.1186/1475-2875-13-43.
Rapid diagnostic tests (RDTs) for malaria provide a practical alternative to light microscopy for malaria diagnosis in resource-limited settings. Three-band RDTs incorporating two parasite antigens may have enhanced diagnostic specificity, relative to two-band RDTs with a single parasite antigen (typically histidine-rich protein 2 [HRP2]).
Phase 1: 2,000 children, two months to five years of age, admitted to a referral hospital in Jinja, Uganda, with acute febrile illness were enrolled. A WHO highly rated three-band RDT was compared to light microscopy of thick peripheral blood films read by local expert microscopists.Phase 2: the three-band RDT was used as a screening tool for inclusion of patients in a clinical trial, and subjects with three positive RDT bands were tested by microscopy using blood samples drawn in parallel. Discordant results were adjudicated by PCR.
Phase 1: 1,648 children had both a RDT and peripheral blood smear performed. The specificity of a RDT with all three bands positive was 82% (95% CI: 79-85%) compared to 62% (95% CI: 59-66%) for HRP2 alone. The sensitivity was 88% (95% CI: 85-89%) and 94% (95% CI: 92-95%) for three-band positive RDT and HRP2 antigen, respectively. 119 patients (7.2%) had a positive HRP2 band, but negative parasite lactate dehydrogenase (pLHD) band and negative peripheral smear, and 72 (61%) of these had received pre-treatment with anti-malarials, suggesting a false positive HRP2 result (p = 0.002).Phase 2: the positive predictive value (PPV) of the three-band RDT was 94% (95% CI 89%-97%) using microscopy as the reference standard. However, microscopy-discordant results were shown to be positive for P. falciparum by PCR in all cases, suggesting that the PPV was in fact higher.
The pLDH antigen on three-band RDTs, used in combination with HRP2, provides added diagnostic specificity for malaria parasitaemia and may be useful to distinguish acute infection from recently treated infection. In situations where diagnostic specificity is desirable (e.g., for selection of malaria-infected participants in clinical trials), a three-band RDT should be considered in a sub-Saharan African setting.
疟疾快速诊断检测（RDTs）为资源有限环境下的疟疾诊断提供了一种实用的替代光学显微镜检查的方法。与包含单一寄生虫抗原（通常为富含组氨酸蛋白2 [HRP2]）的双条带RDT相比，包含两种寄生虫抗原的三条带RDT可能具有更高的诊断特异性。
第一阶段：招募2000名年龄在2个月至5岁之间、因急性发热性疾病入住乌干达金贾一家转诊医院的儿童。将一种世界卫生组织高度评价的三条带RDT与由当地专家显微镜检查人员读取的厚血膜外周血涂片的光学显微镜检查进行比较。第二阶段：将三条带RDT用作筛选工具，以纳入一项临床试验的患者，并使用平行采集的血样通过显微镜检查对RDT三条带均为阳性的受试者进行检测。不一致的结果通过聚合酶链反应（PCR）判定。
第一阶段：1648名儿童同时进行了RDT和外周血涂片检查。所有三条带均为阳性的RDT的特异性为82%（95%可信区间：79 - 85%），而单独的HRP2为62%（95%可信区间：59 - 66%）。三条带阳性的RDT和HRP2抗原的敏感性分别为88%（95%可信区间：85 - 89%）和94%（95%可信区间：92 - 95%）。119名患者（7.2%）HRP2条带为阳性，但寄生虫乳酸脱氢酶（pLHD）条带为阴性且外周血涂片为阴性，其中72名（61%）患者接受过抗疟药预处理，提示HRP2结果为假阳性（p = 0.002）。第二阶段：以显微镜检查为参考标准，三条带RDT的阳性预测值（PPV）为94%（95%可信区间89% - 97%）。然而，PCR显示所有显微镜检查结果不一致的情况在所有病例中恶性疟原虫均为阳性，这表明PPV实际上更高。
三条带RDT上的pLDH抗原与HRP2联合使用，可为疟原虫血症提供额外的诊断特异性，可能有助于区分急性感染与近期接受治疗的感染。在需要诊断特异性的情况下（例如，在撒哈拉以南非洲地区选择临床试验中感染疟疾的参与者），应考虑使用三条带RDT。
